Drug dose cartridge for an inhaler device

ABSTRACT

Devices and methods are described for preparing, managing, and/or administering metered doses of substances for vaporized administration. In some embodiments, dose cartridges comprising at least one botanical substance include a heating element integrated into the cartridge in close contact with the botanical substance. In some embodiments, cartridge-mounted doses are stored in a magazine, optionally in carousel form, before use. Transport of a cartridge from a magazine to an electrically operated vaporizing chamber which activates the heating element is provided by a mechanical pickup means.

RELATED APPLICATIONS

This application is a Continuation of PCT Patent Application No.PCT/IL2015/050677 filed on Jun. 30, 2015, which claims the benefit ofpriority under 35 USC §119(e) of U.S. Provisional Patent ApplicationNos. 62/019,225 filed on Jun. 30, 2014, 62/035,588 filed on Aug. 11,2014, 62/085,772 filed on Dec. 1, 2014, 62/086,208 filed on Dec. 2, 2014and 62/164,710 filed on May 21, 2015.

PCT Patent Application No. PCT/IL2015/050677 was co-filed on Jun. 30,2015 with PCT Patent Application Nos. PCT/IL2015/050673,PCT/IL2015/050678, PCT/IL2015/050676, PCT/IL2015/050674 andPCT/IL2015/050675. The contents of the above applications are allincorporated by reference as if fully set forth herein in theirentirety.

FIELD AND BACKGROUND OF THE INVENTION

The present disclosure, in some embodiments thereof, relates topulmonary delivery of a substance using a personal inhaler device and,more particularly, but not exclusively, to dosage manufacture andhandling for administration.

U.S. Pat. No. 5,655,520 teaches: “A nebulizer is improved by placing aflexible valve in the ambient air inlet tube. Inhalation suction andVenturi effect shut down the flexible valve in proportion to thestrength of the inhalation. Thus, the same output flow rate is obtainedeven with variable strength inhalations. Medications can be properlyadministered by controlled inhalation flow rates. In an alternateembodiment a metered dose inhaler (MDI) is outfitted with a similarflexible valve. Once again the patient is forced to inhale at a constantflow rate, thus causing the medication to seep deeply into the lungs. Inboth embodiments the flexible valve is preferably shaped in a duckbilled fashion with air flow flowing toward the narrow end of the duckbill.”

SUMMARY OF THE INVENTION

According to an aspect of some embodiments, there is provided a dosecartridge for an inhaler device, the dose cartridge comprising: a flatpallet of airflow-permeable material including a heat-vaporizing drugsubstance, the pallet having two opposing faces and being positioned inthe dose cartridge so as to expose the two faces to airflow; asupporting member coupled to the pallet to support the pallet from atleast one side of the pallet joining the two faces; and an electricallyresistive heating element extending at least partially across at leastone of the two opposing faces from an attachment with the supportingmember.

According to some embodiments, the supporting member frames at least aportion of at least three sides of the pallet.

According to some embodiments, the supporting member extends between thetwo faces of the pallet along an edge of the pallet.

According to some embodiments, the resistive heating element is inthermal contact with and extends across at least two opposite surfacesof the pallet.

According to some embodiments, the resistive heating element comprises aU-shape with two ends around a hollow in which the pallet is positioned.

According to some embodiments, an electrical current flows across thetwo opposite surfaces when a voltage is applied between the two ends.

According to some embodiments, the resistive heating element comprisesat least two resistive heating elements, wherein each resistive heatingelement is in thermal contact with and extends across at least a portionof the pallet.

According to some embodiments, the at least two resistive heatingelements extend across opposite surfaces of the pallet.

According to some embodiments, the resistive heating element has aportion encased and extending within at least a portion of the pallet.

According to some embodiments, the resistive heating element extendsacross a surface of the pallet, and comprises a plurality of protrusionsinto the pallet.

According to some embodiments, at least a portion of the resistiveheating element extending across the pallet is permeable to the passageof air.

According to some embodiments, a portion of the resistive heatingelement extending across the pallet comprises a barrier which prevents agranulate portion of the pallet from leaving the inhaler dose cartridge.

According to some embodiments, the resistive heating unit comprises awoven mesh.

According to some embodiments, the resistive heating unit comprises atleast one ribbon of etched metal foil.

According to some embodiments, the at least one ribbon of etched metalfoil is backed by a polymer backing comprising a plurality ofperforations making it permeable to the passage of air.

According to some embodiments, the at least one ribbon of etched metalfoil comprises a narrowed region having elevated resistance, which meltsto break electrical continuity along the at least one ribbon duringdissipation of electrical power applied after release theheat-vaporizing drug substance.

According to some embodiments, the at least one ribbon of etched metalfoil is attached to a fuse element configured to break electricalcontinuity along the at least one ribbon during dissipation ofelectrical power applied after release the heat-vaporizing drugsubstance.

According to some embodiments, at least a portion of the resistiveheating element is embedded in the pallet.

According to some embodiments, the air-permeable support member issufficiently closed to prevent a granulate portion of the pallet fromleaving the inhaler dose cartridge.

According to some embodiments, the air-permeable support memberseparates the pallet and the heating element.

According to some embodiments, the material comprises cannabis.

According to some embodiments, the material comprises at least onebotanical substance selected from the group consisting of Cannabissativa, Cannabis indica, Cannabis ruderalis, Acacia spp., Amanitamuscaria, Yage, Atropa belladonna, Areca catechu, Brugmansia spp.,Brunfelsia latifolia, Desmanthus illinoensis, Banisteriopsis caapi,Trichocereus spp., Theobroma cacao, Capsicum spp., Cestrum spp.,Erythroxylum coca, Solenostemon scutellarioides, Arundo donax, Coffeaarabica, Datura spp., Desfontainia spp., Diplopterys cabrerana, Ephedrasinica, Claviceps purpurea, Paullinia cupana, Argyreia nervosa,Hyoscyamus niger, Tabernanthe iboga, Lagochilus inebriens, Justiciapectoralis, Sceletium tortuosum, Piper methysticum, Catha edulis,Mitragyna speciosa, Leonotis leonurus, Nymphaea spp., Nelumbo spp.,Sophora secundiflora, Mucuna pruriens, Mandragora officinarum, Mimosatenuiflora, Ipomoea violacea, Psilocybe spp., Panaeolus spp., Myristicafragrans, Turbina corymbosa, Passiflora incarnata, Lophophorawilliamsii, Phalaris spp., Duboisia hopwoodii, Papaver somniferum,Psychotria viridis, spp., Salvia divinorum, Combretum quadrangulare,Trichocereus pachanoi, Heimia salicifolia, Stipa robusta, Solandra spp.,Hypericum perforatum, Peganum harmala, Tabernaemontana spp., Camelliasinensis, Nicotiana tabacum, Nicotiana rustica, Virola theidora,Voacanga africana, Lactuca virosa, Artemisia absinthium, Rexparaguariensis, Anadenanthera spp., Corynanthe yohimbe, Caleazacatechichi, Coffea spp. (Rubiaceae), Sapindaceae spp., Camellia spp.,Malvaceae spp., Aquifoliaceae spp., Hoodia spp. Chamomilla recutita,Passiflora incarnate, Camellia sinensis, Mentha piperita, Menthaspicata, Rubus idaeus, Eucalyptus globulus, Lavandula officinalis,Thymus vulgaris, Melissa officinalis, Tobacco, Aloe Vera, Angelica,Anise, Ayahuasca (Banisteriopsis caapi), Barberry, Black Horehound, BlueLotus, Burdock, Camomille/Chamomile, Caraway, Cat's Claw, Clove,Comfrey, Corn Silk, Couch Grass, Damiana, Damiana, Dandelion, Ephedra,Eucalyptus, Evening Primrose, Fennel, Feverfew, Fringe Tree, Garlic,Ginger, Ginkgo, Ginseng, Goldenrod, Goldenseal, Gotu Kola, Green Tea,Guarana, Hawthorn, Hops, Horsetail, Hyssop, Kola Nut, Kratom, Lavender,Lemon Balm, Licorice, Lion's Tail (Wild Dagga), Maca Root, Marshmallow,Meadowsweet, Milk Thistle, Motherwort, Passion Flower, Passionflower,Peppermint, Prickly Poppy, Purslane, Raspberry Leaf, Red Poppy, Sage,Saw Palmetto, Sida Cordifolia, Sinicuichi (Mayan Sun Opener), Spearmint,Sweet Flag, Syrian Rue (Peganum harmala), Thyme, Turmeric, Valerian,Wild Yam, Wormwood, Yarrow, Yerba Mate, and Yohimbe.

According to some embodiments, the electrically resistive heatingelement comprises an electrode contact-receiving region on either sideof a region extending across the pallet.

According to some embodiments, the inhaler dose cartridge comprises aplurality of heating element regions, each region being separatelyconfigured to receive electric current.

According to some embodiments, the plurality of heating elements isassociated with a corresponding plurality of pallets.

According to some embodiments, the resistive heating element comprisesan attachment element, shaped for attachment to the transport arm of adose puller.

According to some embodiments, at least a portion of the dose cartridgeis configured to allow a flow through the pallet at a rate of at least0.5 liters of gas per minute under a pulling vacuum of at least 1 kPa.

According to some embodiments, the supporting member is surrounded bythe pallet where it extends between the two faces of the pallet.

According to some embodiments, the supporting member comprises a hollowregion open on at least one of the two faces.

According to some embodiments, the resistive heating element is a metalresistive heating element.

According to an aspect of some embodiments, there is provided a methodof manufacturing an inhaler dose cartridge for pulmonary delivery of aheat-vaporizing drug substance, comprising: preparing a pallet ofmaterial comprising the heat-vaporizing drug substance; attaching thepallet to a supporting member extending between the two faces of thepallet; and attaching an electrically resistive heating element to thepallet.

According to some embodiments, the preparing the pallet comprises:placing a granulated botanical substance within a dose chamber on aplanar surface; and leveling the botanical substance within the dosechamber.

According to some embodiments, preparing the pallet comprises: placing agranulated botanical substance within a dose chamber on a planarsurface; vibrating the planar surface until the granulated botanicalsubstance is leveled; and pressing the leveled botanical substance,reducing the volume thereof by at least 50% to form a pallet.

According to some embodiments, preparing the pallet comprises cutting atape section from a botanical substance formed into a tape.

According to some embodiments, preparing the pallet comprises loading anair permeable granulated botanical material with a gel, fluid or powdercomprising the heat-vaporizing drug substance.

According to some embodiments, the material comprises cannabis.

According to some embodiments, the material comprises at least onebotanical substance selected from the group consisting of Cannabissativa, Cannabis indica, Cannabis ruderalis, Acacia spp., Amanitamuscaria, Yage, Atropa belladonna, Areca catechu, Brugmansia spp.,Brunfelsia latifolia, Desmanthus illinoensis, Banisteriopsis caapi,Trichocereus spp., Theobroma cacao, Capsicum spp., Cestrum spp.,Erythroxylum coca, Solenostemon scutellarioides, Arundo donax, Coffeaarabica, Datura spp., Desfontainia spp., Diplopterys cabrerana, Ephedrasinica, Claviceps purpurea, Paullinia cupana, Argyreia nervosa,Hyoscyamus niger, Tabernanthe iboga, Lagochilus inebriens, Justiciapectoralis, Sceletium tortuosum, Piper methysticum, Catha edulis,Mitragyna speciosa, Leonotis leonurus, Nymphaea spp., Nelumbo spp.,Sophora secundiflora, Mucuna pruriens, Mandragora officinarum, Mimosatenuiflora, Ipomoea violacea, Psilocybe spp., Panaeolus spp., Myristicafragrans, Turbina corymbosa, Passiflora incarnata, Lophophorawilliamsii, Phalaris spp., Duboisia hopwoodii, Papaver somniferum,Psychotria viridis, spp., Salvia divinorum, Combretum quadrangulare,Trichocereus pachanoi, Heimia salicifolia, Stipa robusta, Solandra spp.,Hypericum perforatum, Peganum harmala, Tabernaemontana spp., Camelliasinensis, Nicotiana tabacum, Nicotiana rustica, Virola theidora,Voacanga africana, Lactuca virosa, Artemisia absinthium, Rexparaguariensis, Anadenanthera spp., Corynanthe yohimbe, Caleazacatechichi, Coffea spp. (Rubiaceae), Sapindaceae spp., Camellia spp.,Malvaceae spp., Aquifoliaceae spp., Hoodia spp. Chamomilla recutita,Passiflora incarnate, Camellia sinensis, Mentha piperita, Menthaspicata, Rubus idaeus, Eucalyptus globulus, Lavandula officinalis,Thymus vulgaris, Melissa officinalis, Tobacco, Aloe Vera, Angelica,Anise, Ayahuasca (Banisteriopsis caapi), Barberry, Black Horehound, BlueLotus, Burdock, Camomille/Chamomile, Caraway, Cat's Claw, Clove,Comfrey, Corn Silk, Couch Grass, Damiana, Damiana, Dandelion, Ephedra,Eucalyptus, Evening Primrose, Fennel, Feverfew, Fringe Tree, Garlic,Ginger, Ginkgo, Ginseng, Goldenrod, Goldenseal, Gotu Kola, Green Tea,Guarana, Hawthorn, Hops, Horsetail, Hyssop, Kola Nut, Kratom, Lavender,Lemon Balm, Licorice, Lion's Tail (Wild Dagga), Maca Root, Marshmallow,Meadowsweet, Milk Thistle, Motherwort, Passion Flower, Passionflower,Peppermint, Prickly Poppy, Purslane, Raspberry Leaf, Red Poppy, Sage,Saw Palmetto, Sida Cordifolia, Sinicuichi (Mayan Sun Opener), Spearmint,Sweet Flag, Syrian Rue (Peganum harmala), Thyme, Turmeric, Valerian,Wild Yam, Wormwood, Yarrow, Yerba Mate, and Yohimbe.

According to some embodiments, the granulated botanical substancecomprises botanical substance having maintained its microstructureintact.

According to some embodiments, the preparing a pallet comprises freezinga botanical substance, and grinding the frozen botanical substance togranulate it, wherein the grinding is substantially without breaking themicrostructure of the botanical substance.

According to some embodiments, the unbroken microstructure comprises atleast 90% of vacuoles containing the drug substance remaining unbrokenafter granulation.

According to some embodiments, preparing the pallet comprises loading anair permeable material with a gel, fluid or powder comprising theheat-vaporizing drug substance.

According to some embodiments, the attaching the pallet to a supportingmember is performed during formation of the pallet.

According to an aspect of some embodiments, there is provided an inhalerdose cartridge for pulmonary delivery of a heat-vaporizing drugsubstance to a user comprising: an airflow-permeable pallet of amaterial comprising the heat-vaporizing drug, wherein the pallet isoriented within the dose cartridge such that it is subjected to airflowthrough the pallet between two face surfaces of thereof; a supportingmember extending between the two faces of the pallet; and an airflowpermeable retaining element extending across at least one of the twoface surfaces and connected to the supporting member.

According to some embodiments, the material of the pallet comprisesfriable material.

According to some embodiments, the friable material comprises botanicalsubstance having intact microstructure of the natural botanicalsubstance.

According to some embodiments, the inhaler dose cartridge comprises anelectrically resistive heating element in thermal communication with thepallet.

According to some embodiments, the electrically resistive heatingelement extends across at least one of the two face surfaces.

According to some embodiments, the airflow permeable retaining elementcomprises the electrically resistive heating element.

According to some embodiments, the inhaler dose cartridge comprises aframe element which at least partially surrounds the pallet on one ormore sides adjacent to the retaining element.

According to some embodiments, the frame element comprises an apertureinto which the pallet of material is fittingly pressed.

According to some embodiments, the frame element comprises a polymerresistant to heat at the temperature at which the heat-vaporizing drugsubstance vaporizes.

According to some embodiments, the frame element is attached to theresistive heating element by at least partial melting of the polymerframe, such that material of the polymer frame flows into one or moreapertures in the resistive heating element.

According to some embodiments, the electrically resistive heatingelement is at least partially embedded in a portion of the frameelement.

According to some embodiments, the electrically resistive heatingelement is at least partially embedded in the pallet.

According to some embodiments, the frame element comprises a transportarm interlock region, shaped for attachment to the transport arm of adose puller.

According to an aspect of some embodiments, there is provided a clampingchamber for an inhaler dose cartridge for pulmonary delivery of aheat-vaporizing drug substance to a user comprising: a cartridgetransport configured to move the inhaler dose cartridge from a storageposition into a use position; a holder for holding a dose cartridge suchthat a heat-vaporizing drug substance is in sealed alignment with an airconduit of the clamping chamber; and electrodes positioned to be inelectrical contact with at least two electrical contact receivingregions of an electrically resistive heating element of an inhaler dosecartridge in the clamping chamber.

According to some embodiments, the cartridge transport comprises a dosepulling arm, shaped to interlock with a receiving region of the dosecartridge such that movement of the dose pulling arm moves a dosecartridge into or out of the use position.

According to some embodiments, the sealed alignment defines a pathwaythrough a pallet of material within a lumen along which air passingthrough the pallet continues to an exit aperture leading to thepulmonary organs of the user.

According to some embodiments, the holder comprises the cartridgetransport configured to move the inhaler dose cartridge.

According to some embodiments, the clamping chamber comprises: aplurality of the cartridge transports each configured to move acorresponding inhaler dose cartridge; a plurality of holderscorresponding to the plurality of cartridge transports; andcorresponding electrodes for each of the cartridge transports.

According to some embodiments, the plurality of holders is positionedsequentially along the air conduit such that airflow through one of theheld dose cartridges passes through the other.

According to some embodiments, the plurality of holders is positionedsuch that each holder receives a separate airflow.

According to some embodiments, the air conduit comprises a plurality oflumens corresponding to the plurality of holders, and each of theholders is positioned in a separate one of the plurality of lumens.

According to some embodiments, each of the holders is positioned in ashared lumen of the air conduit.

According to some embodiments, at least one of the holders is operableto position a blocker which at least partially blocks airflow throughthe position where a dose cartridge is held.

According to some embodiments, the cartridge transport is configured tomove any a plurality of inhaler dose cartridges to one of the pluralityof holders.

According to an aspect of some embodiments, there is provided an inhalerdevice comprising the clamping chamber above.

According to an aspect of some embodiments, there is provided an inhalerdevice comprising two or more of the clamping chambers above.

According to some embodiments, the inhaler device comprises a dosecartridge dispenser comprising a plurality of dose cartridges within aclosed container.

According to some embodiments, the plurality of dose cartridges comprisedose cartridges differing in at least one from among the groupconsisting of drug substance amount, drug substance concentration, anddrug substance composition.

According to some embodiments, the inhaler device comprises a controllerconfigured to select a dose cartridge from the plurality of dosecartridges in accordance with a dosing regimen.

According to some embodiments, the controller is configured to adjustthe dosing regimen according to a progress of the regimen.

According to an aspect of some embodiments, there is provided a dosecartridge dispenser comprising a plurality of dose cartridges within aclosed container, and including an interlock which, after dispensing ofa first dose cartridge from the container, prevents dispensing of asecond dose cartridge from the container until the first dose cartridgeis returned to the dispenser.

According to some embodiments, the dose cartridge is dispensed to asubstance vaporizing unit, and the operation of the interlock comprisesinserting the substance vaporizing unit into the dose cartridgedispenser.

According to an aspect of some embodiments, there is provided avaporizer device, comprising: a compartment sized to fittingly receive adose cartridge from a dose cartridge container while the vaporizerdevice is fitted to the dose cartridge container, and a power unitoperable, while the vaporizer device is removed from the dose cartridgecontainer, to deliver current to a heating element of the fittinglyreceived dose cartridge, for volatilization of a volatilizing substancecontained by the dose cartridge.

According to some embodiments, the vaporizer device includes the dosecartridge container, the dose cartridge container containing a pluralityof the dose cartridges.

Unless otherwise defined, all technical and/or scientific terms usedherein have the same meaning as commonly understood by one of ordinaryskill in the art to which the invention pertains. Although methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of embodiments of the invention, exemplarymethods and/or materials are described below. In case of conflict, thepatent specification, including definitions, will control. In addition,the materials, methods, and examples are illustrative only and are notintended to be necessarily limiting.

As will be appreciated by one skilled in the art, aspects of the presentinvention may be embodied as a system, method or computer programproduct. Accordingly, aspects of the present invention may take the formof an entirely hardware embodiment, an entirely software embodiment(including firmware, resident software, micro-code, etc.) or anembodiment combining software and hardware aspects that may allgenerally be referred to herein as a “circuit,” “module” or “system.”Furthermore, some embodiments of the present invention may take the formof a computer program product embodied in one or more computer readablemedium(s) having computer readable program code embodied thereon.Implementation of the method and/or system of some embodiments of theinvention can involve performing and/or completing selected tasksmanually, automatically, or a combination thereof. Moreover, accordingto actual instrumentation and equipment of some embodiments of themethod and/or system of the invention, several selected tasks could beimplemented by hardware, by software or by firmware and/or by acombination thereof, e.g., using an operating system.

For example, hardware for performing selected tasks according to someembodiments of the invention could be implemented as a chip or acircuit. As software, selected tasks according to some embodiments ofthe invention could be implemented as a plurality of softwareinstructions being executed by a computer using any suitable operatingsystem. In an exemplary embodiment of the invention, one or more tasksaccording to some exemplary embodiments of method and/or system asdescribed herein are performed by a data processor, such as a computingplatform for executing a plurality of instructions. Optionally, the dataprocessor includes a volatile memory for storing instructions and/ordata and/or a non-volatile storage, for example, a magnetic hard-diskand/or removable media, for storing instructions and/or data.Optionally, a network connection is provided as well. A display and/or auser input device such as a keyboard or mouse are optionally provided aswell.

Any combination of one or more computer readable medium(s) may beutilized for some embodiments of the invention. The computer readablemedium may be a computer readable signal medium or a computer readablestorage medium. A computer readable storage medium may be, for example,but not limited to, an electronic, magnetic, optical, electromagnetic,infrared, or semiconductor system, apparatus, or device, or any suitablecombination of the foregoing. More specific examples (a non-exhaustivelist) of the computer readable storage medium would include thefollowing: an electrical connection having one or more wires, a portablecomputer diskette, a hard disk, a random access memory (RAM), aread-only memory (ROM), an erasable programmable read-only memory (EPROMor Flash memory), an optical fiber, a portable compact disc read-onlymemory (CD-ROM), an optical storage device, a magnetic storage device,or any suitable combination of the foregoing. In the context of thisdocument, a computer readable storage medium may be any tangible mediumthat can contain, or store a program for use by or in connection with aninstruction execution system, apparatus, or device.

A computer readable signal medium may include a propagated data signalwith computer readable program code embodied therein, for example, inbaseband or as part of a carrier wave. Such a propagated signal may takeany of a variety of forms, including, but not limited to,electro-magnetic, optical, or any suitable combination thereof. Acomputer readable signal medium may be any computer readable medium thatis not a computer readable storage medium and that can communicate,propagate, or transport a program for use by or in connection with aninstruction execution system, apparatus, or device.

Program code embodied on a computer readable medium and/or data usedthereby may be transmitted using any appropriate medium, including butnot limited to wireless, wireline, optical fiber cable, RF, etc., or anysuitable combination of the foregoing.

Computer program code for carrying out operations for some embodimentsof the present invention may be written in any combination of one ormore programming languages, including an object oriented programminglanguage such as Java, Smalltalk, C++ or the like and conventionalprocedural programming languages, such as the “C” programming languageor similar programming languages. The program code may execute entirelyon the user's computer, partly on the user's computer, as a stand-alonesoftware package, partly on the user's computer and partly on a remotecomputer or entirely on the remote computer or server. In the latterscenario, the remote computer may be connected to the user's computerthrough any type of network, including a local area network (LAN) or awide area network (WAN), or the connection may be made to an externalcomputer (for example, through the Internet using an Internet ServiceProvider).

Some embodiments of the present invention may be described below withreference to flowchart illustrations and/or block diagrams of methods,apparatus (systems) and computer program products according toembodiments of the invention. It will be understood that each block ofthe flowchart illustrations and/or block diagrams, and combinations ofblocks in the flowchart illustrations and/or block diagrams, can beimplemented by computer program instructions. These computer programinstructions may be provided to a processor of a general purposecomputer, special purpose computer, or other programmable dataprocessing apparatus to produce a machine, such that the instructions,which execute via the processor of the computer or other programmabledata processing apparatus, create means for implementing thefunctions/acts specified in the flowchart and/or block diagram block orblocks.

These computer program instructions may also be stored in a computerreadable medium that can direct a computer, other programmable dataprocessing apparatus, or other devices to function in a particularmanner, such that the instructions stored in the computer readablemedium produce an article of manufacture including instructions whichimplement the function/act specified in the flowchart and/or blockdiagram block or blocks.

The computer program instructions may also be loaded onto a computer,other programmable data processing apparatus, or other devices to causea series of operational steps to be performed on the computer, otherprogrammable apparatus or other devices to produce a computerimplemented process such that the instructions which execute on thecomputer or other programmable apparatus provide processes forimplementing the functions/acts specified in the flowchart and/or blockdiagram block or blocks.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

Some embodiments of the invention are herein described, by way ofexample only, with reference to the accompanying drawings. With specificreference now to the drawings in detail, it is stressed that theparticulars shown are by way of example, and for purposes ofillustrative discussion of embodiments of the invention. In this regard,the description taken with the drawings makes apparent to those skilledin the art how embodiments of the invention may be practiced.

In the drawings:

FIG. 1 is a schematic flowchart of a method of preparing a granulatedbotanical substance for use in dose packaging with an inhaler device,according to some embodiments;

FIG. 2 is a schematic flowchart of a method of packaging a botanicalsubstance to a dose cartridge for use with an inhaler device, accordingto some embodiments;

FIG. 3 is a schematic view of a botanical substance grinding apparatus,according to some embodiments;

FIG. 4 is a schematic view of the grinding plate of a botanicalsubstance grinding head, according to some embodiments;

FIGS. 5A-5B are schematic views of a dose cartridge, disassembled andassembled, according to some embodiments;

FIGS. 5C-5M schematically illustrate alternative constructions of dosecartridges, according to some embodiments;

FIGS. 6A-6E schematically illustrate a carousel-type dose deliverysystem for use with an inhaler device, according to some embodiments;

FIGS. 7A-7B schematically illustrate a clamping chamber for heating anddelivery of vaporized substance from a dose cartridge, according to someembodiments;

FIG. 7C schematically illustrates a cross section of a dose cartridgewithin a clamping chamber clamping a cartridge, according to someembodiments;

FIGS. 8A-8B schematically illustrate a dose delivery device for loadingfrom a dose magazine (e.g. a carousel), and separable from the magazinefor delivery of the dose itself, according to some embodiments; and

FIG. 9 schematically illustrates an interlock-protected dose dispensingdevice, together with a removable dose administration assembly,according to some embodiments;

FIG. 10 schematically illustrates a carousel arranged for potentiallysimultaneous administration of substances from a plurality of dosecartridges held within two separate carousel magazines, according tosome embodiments;

FIGS. 11A-11C schematically illustrate a linear-type dose cartridgemagazine for use with an inhaler device, according to some embodiments;

FIG. 12 schematically illustrates a carousel arranged in an inhaler forsimultaneous administration of substances from a plurality of dosecartridge clamping chambers in a corresponding plurality of extractionairflow conduits, according to some embodiments;

FIGS. 13A-13B schematically illustrate a linear-type dose cartridgemagazine and dual-dose cartridge transport in two sequential positions,according to some embodiments; and

FIGS. 13C-13D schematically illustrate the dual-dose cartridge transportof FIGS. 13A-13B in two sequential positions, according to someembodiments.

DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

The present disclosure, in some embodiments thereof, relates topulmonary delivery of a substance using a personal inhaler device and,more particularly, but not exclusively, to dosage manufacture andhandling for administration.

Overview

An aspect of some embodiments relates to processing and packaging of aheat-vaporizing drug substance to a cartridge providing an integratedheating element.

In some embodiments, the heat-vaporizing drug substance comprises acompound having at least one medicinal and/or somatic and/orpsychoactive effect. Optionally the compound includes THC and/ornicotine. In some embodiments, the heat-vaporizing drug substancevaporizes at a temperature requiring a substantial exogenous heat inputto reach a temperature above ambient temperature. For example, thesubstance vaporizes at a temperature within the range from 80° C.-250°C., or within another range having the same, higher, lower, intermediateand/or intermediate bounds. In some embodiments, the substance vaporizesat a temperature above 80° C., 100° C., 150° C., 200° C., 230° C., oranother higher, lower, or intermediate temperature. In some embodiments,the time to reach a volatilizing temperature is, for example, about in arange between about 100 msec-5 sec, 100-750 msec, 150-300 msec, oranother range having the same, larger, smaller, and/or intermediatebounds. In particular, the time is, for example, 250 msec, 500 msec,1000 msec, or another greater, smaller, or intermediate value.

In some embodiments, the heat-vaporizing drug substance is avolatilizing substance distributed throughout a pallet comprising acarrier material. Optionally, the carrier material comprises at leastone botanical substance, such as cannabis, tobacco, and/or other plantmatter. Additionally or alternatively, the carrier material comprises aporous and air-permeable absorptive matrix; for example, a foam, sponge,felt, and/or another fiber matrix, which absorbs the heat-vaporizingdrug substance to fix it into place. In some embodiments, the absorptivematrix is substantially non-friable, providing sufficient strength, forexample, to allow direct attachment of other drug cartridge components,such as a heating element, to or within the absorptive matrix without arequirement for additional mechanical support to preserve the integrityof the absorptive matrix surfaces and/or structure. In some embodiments,the pallet is friable; for example, comprising granules, fibers, oranother fine structure compressed to form the pallet.

In some embodiments, the heating element is an electrically resistiveheating element. Optionally the electrically resistive heating elementconsists of or comprises a metal, for example nichrome, FeCrAl,cupronickel, titanium, and/or stainless steel. Optionally, the heatingelement is packaged in thermal contact with the heat-vaporizing drugsubstance. Thermal contact comprises, for example, being in directcontact, or in contact across a heat-transmitting layer allowing a highrate of thermal transfer (for example, comprised of a high heatconductance material such as copper, aluminum, brass or steel; and/orhaving a thin-walled construction of less than about 10 μm, 20 μm, 25μm, 50 μm, or another greater, lesser or intermediate thickness). Insome embodiments, thermal contact comprises sufficiently closeapposition of pallet and heating element that the pallet subtendssubstantially the whole thermal radiating angle of the portion of theheating element overlying it; for example, more than 90%, 95%, 99%, oranother greater, lesser or intermediate value. In some embodiments, thepeak current applied to the electrode is in the range of about 1-10Amperes; for example, about 1 Amperes, 2 Amperes, 4 Amperes, 6 Amperes,or another higher, lower, or intermediate current.

In some embodiments, the thermal contact comprises the heating elementextending across and in contact with one or more surfaces of the pallet,for example, one side, or two opposite, largest surface-area sides ofthe pallet. In some embodiments, the thermal contact comprises theheating element being at least partially embedded within the pallet.

In some embodiments, the heating element is permeable to the passage ofair. In some embodiments, the pallet is permeable to the passage of air.Permeability is under conditions, for example, of the passage of air atambient temperature through a heated assembly of pallet and heatingelement under a suction pressure such as a suction pressure generated byinhaling, and/or a positive pressure generated from a side away from theinhaling side of the cartridge. In some embodiments, the appliedpressure is in the range of 5-20 mmHg, 10-25 mmHg, 5-30 mmHg, 25-40mmHg, 30-50 mmHg, or another range having the same, higher, lower,and/or intermediate bounds. According to some embodiments, the pallethas an air-permeable structure that allows a flow of at least 0.5 litersof gas per minute or even at least 1 liter of gas per minute under apulling vacuum of at least 1-5 kPa (−1-(−5) kPa). In some embodiments,the pallet has this permeability in its packaged form. In someembodiments, this permeability is reached during heating of the pallet,for example, due to volatilization, drying, melting, and/or burning ofthe pallet constituents.

In some embodiments, the heating element comprises a bend of about 180°,such that the element is formed into a clip- and/or U-shape thatencloses the pallet on at least two sides. Optionally, the heatingelement on the cartridge is positioned so that there is no self-contactbetween the two sides of the U-shape. Optionally, application of currentto the heating element by a dose heating assembly is to or near the twoends (comprising contact-receiving regions) of the U-shape, such thatheating may occur on two sides of the pallet at once. In someembodiments, application of current to the heating element is byconnection to a contact-receiving region on either side of the pallet onone or both sides of the cartridge. The heating element is optionallydivided into two or more parts, each receiving current independently.Alternatively, the heating element is provided as a single piece(optionally, a piece which entirely encloses the pallet); electrodesbeing applicable to contact-receiving regions of the element such that avoltage potential is generated over the extent of the heating element inthermal contact with the pallet.

An aspect of some embodiments relates to the providing of a supportmember along with the pallet and heating element.

In some embodiments, the support member comprises a frame, or a portionof a frame. Optionally, the frame comprises an aperture for receivingmaterial of the pallet (a “dose chamber”). In some embodiments, thesurface area over the width and length of the dose chamber is in therange of about 20-100 mm²; for example, about 25 mm², 50 mm², 66 mm², 80mm², 100 mm², or another greater, smaller, or intermediate surface area.In some embodiments, the aperture region is open on one side.Optionally, the open side of the aperture region is closed by theapplication of a U-shaped heating element.

In some embodiments, the frame aperture dimensions are, for example,about 6×10 mm, the frame defining a volume of, for example, about 0.5 mmor about 1 mm thick. In some embodiments, the ratio of a thickness ofthe pallet to a long or short side of the flat face of a pallet isabout, for example, 1:5, 1:10, 1:12, 1:20, or another larger, smaller,or intermediate ratio. Optionally, the aperture area is in the range ofabout 20-100 mm²; for example 20 mm², 40 mm², 50 mm², 60 mm², 80 mm², oranother greater, lesser, or intermediate face area. The aperture isoptionally shaped substantially as a square (for example, about 8×8 mm);optionally the aperture is oblong (for example, rectangular) with a sideratio of, for example, 1:2, 1:3, 1:4, 1:10, or another larger, smaller,or intermediate ration of side lengths. Optionally, the aperture is, forexample, about 30×2 mm in dimension.

In some embodiments, the support member comprises a connection betweenstructures which extend across one or both of the flattened faces of thepallet. For example, the support member is positioned at least partiallyaround or alongside the pallet, and one or more other structures extendsfrom an attachment to the support member across a flattened face of thepallet. Optionally, the support member extends at least partially withinthe body of the pallet itself. Optionally, the support member isattached on at least one side to an electrically resistive heatingelement, and/or a barrier permeable to airflow but configured to retainfragments of the pallet. In some embodiments, a support member providesa potential advantage for the containment of an optionally fragilepallet, by linking further supporting and/or enclosing structures to oneanother so that a space for containing the material of the pallet isdefined without depending on the mechanical integrity of the palletitself to hold together. In some embodiments, the support member extendsalong 1, 2, 3, or 4 sides of the pallet.

Optionally, extending along four sides comprises an enclosing frame,while extent along fewer sides comprises a partially open frame which isoptionally closed by another element of the chamber. Optionally, asupport member extending along one side comprises an anchor throughwhich elements of the cartridge are coupled to one another. In someembodiments, the support member avoids blocking exposure of the palletto airflow by covering less than 20% of any of the flattened faces ofthe pallet. In some embodiments, the blocked exposure is less than 30%,less than 10%, less than 5%, or another greater, smaller, orintermediate amount.

In some embodiments, the support member and/or aperture performs one ormore of the following functions:

-   -   positions the pallet at a reproducible position relative to the        overall dimensions of the cartridge;    -   provides mechanical stability to the pallet (for example,        support at one or more edges, rigidity to resist bending, and/or        anchoring);    -   provides attachment elements (e.g. latching/anchoring elements        and/or surfaces) enabling the transport of the cartridge by        mechanical elements shaped to interact with the cartridge;    -   provides insulation between two parallel sides of the heating        element to prevent self-contact; and/or    -   provides surface region and/or bulk volume region for        adherence/anchoring/embedding of the heating element with the        cartridge.

In some embodiments, general functions of the frame and/or apertureinclude shaping of the dose structure during manufacture, and/orassistance in manipulation of the dose for administration.

In some embodiments, the material forming the pallet is friable. In someembodiments, for example, the pallet is formed from small adheringparticles such a granulated botanical substance. While this is apotential advantage, for example, for increased porosity and/or tomaintain microstructure of the original botanical substance (thuspotentially helping to preserve drug substances from deterioration), theresulting structure is potentially fragile. In some embodiments, themaintained microstructure includes one or more of: cell walls, vacuolemembranes, plastid membranes, trichome hairs and/or heads, or anotherplant microstructure, and in particular, a plant microstructure whichencapsulates one or more drug substances.

In some embodiments, at least 50% of a target microstructure(microstructure encapsulating a drug substance) is preserved duringgranulation. In some embodiments, the proportion of preserved targetmicrostructure is at least 60%, 70%, 80%, 90%, 95%, 99%, or anotherlarger, smaller, or intermediate proportion. In some embodiments, thepallet material is supported on one or both faces by a porous supportstructure, for example a mesh, perforated membrane, or anotherstructure. The support structure is optionally porous enough to permitthe passage of air, while still preventing the loss of particles fromthe friable pallet. In some embodiments, the pallet face supportstructure comprises a heating element. In some embodiments, the palletface support structure comprises a polymer membrane, a fabric (forexample, a woven mesh), or another flat, air-permeable support structurewhich covers the friable face of the pallet. In some embodiments, thepallet face support structure is positioned between the pallet and theheating element. Optionally, the heating element is positioned betweenthe pallet and the pallet face support structure.

In some embodiments, the frame comprises a polymer or ceramic which issubstantially heat resistant (for example, non-burning, non-melting,dimensionally stable) at the temperature of volatilization. In someembodiments, the polymer comprises, for example, a liquid crystalpolymer (LCP), polyether ether ketone (PEEK), Ultem, Teflon, Torlon,Amodel, Ryton, Forton, Xydear, Radel, Udel, polypropylene, Propylux,polysulfone, polyether sulfone, acrylic, ABS, nylon, PLA,polybenzimadazole, polycarbonate, polyetherimide, polyethylene,polyphenylene oxide, polyphenylene sulfide, polystyrene, polyvinylchloride, one or more other thermoplastics, and/or another polymermaterial.

In some embodiments, a latching/anchoring element comprises anattachment element (e.g. transport arm interlock region), shaped forattachment to the transport arm of a dose puller or other dose transportmechanism.

In some embodiments, the granulated portion of the pallet is closedwithin the assembled cartridge by the heating element extending acrossthe aperture to form a barrier against the pallet granules falling fromthe cartridge. In some embodiments, the heating element extends acrossthe aperture without itself closing the aperture (for example, a ribbonheating element is provided having gaps between windings of the ribbon).In some embodiments another element is provided which acts as acontainment barrier (or wall). Optionally, the containment barrier ispositioned over the heating element and pallet together, and/or betweenthe heating element and the pallet.

An aspect of some embodiments relates to a method of manufacturing adrug dose load in the form of a pallet for assembly with an inhaler dosecartridge.

In some embodiments, a measured amount of a powdered or granulatedmaterial containing a drug substance (comprising, for example, agranulated botanical substance), is placed in a dose chamber. In someembodiments, the measured amount is in the range, for example, of about10-100 mg. In some embodiments, the dose chamber is sized such that theextent of the dose pallet, upon formation, is limited by bounds of thedose chamber, for example, bounds of pallet width and length.

In some embodiments, the measured amount of granulated substance isleveled by vibration of the dose chamber. Optionally, the vibrating iswith an amplitude in the range of about 0.1-1.2 mm; for example 0.5 mm.The frequency of vibration is, for example, in the range of about 20-300Hz (such as 30 Hz, 45 Hz, 60 Hz, 75 Hz, or another higher, lower, orintermediate frequency). Duration of shaking is, for example, chosenfrom within the range of 100-1100 msec (such as about 300 msec, 400msec, 500 msec, 800 msec, or another longer, shorter, or intermediatetime). Optionally, the chamber is secured before vibration, to preventgranulate from escaping the chamber from underneath.

In some embodiments, leveling the measured amount of granulate substancecomprises using a rigid member (for example a blade) to wipe across atop surface of the dose cartridge. Optionally, the granulate substanceis pulled into the dose chamber by applying vacuum before using therigid member (for example a blade) to level it in position.

In some embodiments, the pallet is formed from the leveled granulate bycompression by a pressing element. Compression is to a thickness whichis, for example, in the range of 10-50% of the pre-compression thicknessof the distributed granulate mass. Compression is, for example, to about15%, 20%, 30%, 40%, or another larger, smaller, or intermediate value ofthe uncompressed thickness of the distributed granulate mass. In someembodiments, the granulate is compressed to a pallet of thickness withina range of between about 200-1500 μm, or thickness within another rangehaving the same, larger, smaller and/or intermediate bounds.

Additionally or alternatively, pallet formation comprises placing a dosecartridge frame above a leveled granulate layer and using vacuum to pullup granulate material that is positioned immediately below the dose.

In some embodiments two or more leveling and/or pallet formation optionsare utilized for a single dose cartridge.

An aspect of some embodiments relates to positioning of a cartridgecarrying a heat-vaporizing drug substance with integrated heatingelement within a clamping chamber which activates the heating elementwhile confining the volatile components of the vaporizing drug substanceto a substance delivery channel.

In some embodiments, the positioning is effected by movement of thecartridge along a track (for example, by a cartridge transportmechanism). In some embodiments, the chamber comprises at least onestructure which encloses the cartridge on either side to seal it withina defined lumen, and/or makes electrical contact with a heating elementof the cartridge. Optionally, electrical contact is on either side ofthe cartridge. Optionally, electrical contact is made on sides of thecartridge at points defined by the positioning of the cartridge relativeto electrodes of an inhaler device. Optionally, contact pads extend fromthe heating element for the making of electrical contact therewith.Optionally the electrodes and dose cartridge are positioned such thatthe electrodes and the contacts on the cartridge are outside the sealedlumen while all vaporized material is confined to the inside of thelumen.

An aspect of some embodiments relates to a cartridge container for usewith a substance vaporizer which is alternately:

-   -   attached to the cartridge container for receipt of a dose        cartridge into the substance vaporizer; and    -   detached from the cartridge container (magazine) for dose        administration.

In some embodiments, the detachable drug substance vaporizer is used aspart of an interlock mechanism for control of the dispensing of dosecartridges. For example, in some embodiments, the drug substancevaporizer is used as part of the activation of an interlock whichprevents extraction of a new dose cartridge until a previously extractedcartridge is returned to a dispensing container.

Herein, the term “dose cartridge” refers to an assembly intended for alimited number of uses (usually one use, or uses confined within a briefsession of inhalations), and comprising a material (for example, abotanical substance) carrying at least one drug substance, andoptionally including additional elements for the transport, mechanicalstabilization, and/or volatilization or vaporization (by heating, forexample) of the drug substance. In some embodiments, a dose cartridgecomprises drug substance material for deliver over no more than, forexample, 1, 2, 3, or 4 inhalations. Material (optionally, a botanicalsubstance) comprising a drug substance (and/or having a drug substanceadded thereto) and arranged within a dose cartridge is referred toherein as a “drug dose”, “drug dose load” or “pallet”; “pallet” is usedin particular to indicate a drug dose is arranged within or as the dosecartridge in flattened form, so as to be suitable for allowing air to bedrawn through it for extraction of the drug substance. A palletcomprises, for example, a flattened expanse of porous material thinenough to permit airflow through and between the two largest faces.Herein, the term “drug substance” denotes one or more heat-vaporizingdrug substances contained in and/or associated with a pallet forinhalation therefrom by a user.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not necessarily limited in itsapplication to the details of construction and the arrangement of thecomponents and/or methods set forth in the following description and/orillustrated in the drawings. The invention is capable of otherembodiments or of being practiced or carried out in various ways.

Dose Cartridge with Integrated Heating Element

Reference is now made to FIGS. 5A-5B, which are schematic views of adose cartridge 2300, disassembled (FIG. 5A) and assembled (FIG. 5B),according to some embodiments. Reference is also made to FIGS. 5C-5M,which schematically illustrate alternative constructions of dosecartridges 2350, 2360, 2370, 2380, 2390, and 2395, according to someembodiments. FIGS. 5C, 5E, 5G, 5J, and 5L show disassembled dosecartridges. FIGS. 5D, 5F, 5H, 5K, and 5M show assembled dose cartridges.

In some embodiments, drug doses comprising a drug substance areassembled upon and/or within a dose cartridge 2300. Optionally, thecartridge 2300 comprises:

-   -   a drug dose load 2304, optionally formed (for example, by        flattening) for rapid vaporization;    -   mechanical support for the drug dose load 2304 (for example,        support by enclosure within a housing 2301, which is optionally        frame shaped);    -   an attachment element for facilitating transport of the        cartridge 2300 (for example, latch mandibles 2302); and/or    -   means for vaporizing the drug dose load 2304 (for example, an        electrically resistive heating element 2306, optionally a mesh).

Different embodiment examples of the above-listed elements are describedherein, as well as examples of embodiments of assembled dose cartridgeswhich lack at least one of these elements. It is to be understood thatthe different element embodiments are optionally combined in embodimentsof assembled dose cartridges in other combinations as well (for example,any heating element design provided with any frame design).

Optionally, the dose cartridge is disposable. Potential advantages of adisposable cartridge include: containment of drug dose and/or drugsubstance residue for disposal; close integration of dosage support andtransport for reliable dosage transport within a vaporizer device;and/or reduced need to maintain and/or monitor portions of the vaporizerdevice (such as a vaporizing heating element) which are subject toconditions that could degrade performance over time.

Optionally, the dose cartridge is for use in a single inhalation.Potential advantages of a single-use cartridge include improving theprecision and/or reliability in controlling the amount of drug substancevaporized under inhaler settings, as some relating to contamination anduse damage are reduced.

In some embodiments, dose cartridge 2300 comprises a housing 2301 havinga drug dose receiving chamber 2303. Optionally, the housing 2301comprises a flattened and elongated strip; while the chamber 2303comprises an aperture framed or partially frame by the strip. Duringpreparation of the dose cartridge 2300 for dosing, a drug dose load 2304is inserted into receiving chamber 2303. Optionally, the drug dose isformed —before or during insertion—such that it conforms to theflattened shape of the substance receiving chamber 2303. It is apotential advantage for the drug dose to be held in a flattened format(a “pallet”, herein), since a greater surface area and/or a more uniformthickness potentially allow faster and/or more evenly distributedheating and/or airflow during dosage vaporization and delivery.

In some embodiments, the drug dose load or pallet dimensions are, forexample, about 6×10 mm across the exposed surface area, and about 1 mmthick. Optionally, the thickness of the drug dose load is in the rangeof about 0.2-1.0 mm, or a greater, lesser, or intermediate thickness.Optionally, the face area of the drug dose load is in the range of about20-100 mm²; for example 20 mm², 40 mm², 50 mm², 60 mm², 80 mm², oranother greater, lesser, or intermediate face area. The substance loadis optionally formed into a square or substantially square pallet (forexample, about 8×8×1 mm); optionally the pallet is oblong with a sideratio of, for example, 1:2, 1:3, 1:4, 1:10, or another larger, smaller,or intermediate ration of side lengths. Optionally, the pallet is, forexample, about 30×2×1 mm in dimension. Corresponding dosing load byweight is about 15 mg in some embodiments. In some embodiments, thedosing load is selected from within a range of about 10-100 mg, oranother range having the same, larger, smaller, and/or intermediatebounds.

It is a potential advantage to at least partially surround the drug doseload 2304 with a framing housing 2301 for greater mechanical stability.For example, botanical substances used to form a drug dose potentiallycomprise friable material, such that a drug dose load 2304 is liable toshed particles, particularly if bent and/or agitated. Enclosure within acartridge frame allow the drug dose load 2304 to be moved within thesystem without applying stresses directly to the drug dose load 2304itself and/or optionally renders it less sensitive to agitation. In someembodiments, the overall length and width of the cartridge is about20×10 mm, or another larger, smaller, or intermediate size. Duringmanufacture, a framing housing is a potential advantage for formation ofa pallet of the correct size for fitted occlusion of a conduit throughwhich air flows to pick up volatiles released during heating of thepallet.

It is to be understood that completely surrounding the pallet is notrequired, in some embodiments, to achieve sufficient mechanicalstability. For example, in some embodiments (FIGS. 5E-5F), a drug doseload 2304 is placed in an open-sided chamber 2363 defined by a “U”shaped frame portion 2361. Potentially, this allows packing the materialof drug dose load 2304 into the cartridge 2360 from the open side offrame portion 2361. Potentially, the “U” shaped frame simplifies and/orspeeds molding and/or release of the frame itself during manufacture. Insome embodiments, the open side is closed off, for example, by astructure such as resistive heating element 2306, a permeable overlay2375 (optionally a retaining mesh; FIG. 5G), or another structure.

In some embodiments, other support of a pallet is provided. A completelyframeless example is shown, for example, in cartridge 2390A of FIG. 5L,where the whole extent of frame 2391A (optionally including even latchmandible 2392) is provided by the pallet material. In some embodiments,pallet material is sufficiently stable when prepared that no orrelatively little additional mechanical support is required for use (forexample, the pallet is compressed so that it remains intact duringtransport between a magazine and a clamping chamber). Optionally, atleast a portion of the pallet material is mixed with a binder to addstability. Optionally, the pallet is a one piece pallet havingsufficient stability, and which serves to hold a gel, fluid or powdercomprising the heat-vaporizing drug substance.

In some embodiments, a one-piece pallet/frame is formed, optionally witha plurality of pallet materials, for example, a frame material for theregion of frame 2391A (which may or may not comprise active substance),and a material containing drug substance for release in pallet region2394A. Additionally or alternatively, the conditions of formation (forexample, degree of compression packing) are different between theframing portion of the pallet, and the drug substance releasing portionof the pallet. In some embodiments, the drug substance releasingmaterial covers, for example, about 60 mm² near the center of the pallet2393. A drug substance releasing material is a drug substance-containingmaterial, which releases that material, for example, in response toheating by a heating element 2306 located within and/or alongside it. Insome embodiments, a heating element 2306 also provides mechanicalsupport. Optionally, the pallet/frame assembly 2393 in turn provideselectrical insulation between parts of the heating element 2306.Attachment between heating element 2306 and pallet 2393 is, for example,by using any method known in the art that would remain stable duringuse, including, for example, one or more of welding, glue, cold press,hot press and/or pins.

In some embodiments (for example, cartridge 2395 of FIG. 5M), a pallet2399 is provided with perforations 2398 which increase its permeabilityto flow. This is of particular potential benefit for frameless or nearlyframeless cartridge embodiments. Pallet 2399 of dose cartridge 2395, forexample, is bounded only by latch mandible 2396 (which is optionallyformed as an integral part of the pallet) and (transparently drawn) “U”shaped heating element 2306. Potentially, packing pallet material withsufficient density to achieve mechanical self-stability reduces theairflow permeability of the resulting pallet, thus interfering with drugvolatilization. Perforations 2398 are provided, for example, byintroducing gaps with the tooling (a mold, for example) used in packingthe bioactive material, by perforating the pallet after formation, or byanother method.

In some embodiments, (cartridge 2390 of FIGS. 5J-5K), the mandibles 2391are provided as a separate part (for example, manufactured of polymer ormetal), attached to a pallet 2394 of material (for example, one or morebotanical substances) comprising the drug substance to be released. Insome embodiments, a heating element 2306 or another wrapping structureprovides additional mechanical support. Optionally, attachment of pallet2394 to mandibles 2391 comprises use of an adhesive. Optionally,attachment comprises mechanical interconnection; for example, one of themandibles 2391 and pallet 2394 is formed with a tab, and the other witha slot, and/or the mandibles 2391 are provided with protrusions (forexample, a comb of spikes) around which the pallet 2394 is formed.

In some embodiments (e.g. the cross section of dose cartridge 2380 shownin FIG. 51), a heating element 2386 which wraps a pallet 2304 is weldedat a join 2381 where two sides of the heating element come together.Potentially, this provides an advantage for providing additionalmechanical stability to a pallet 2304 (and particularly, for one of theframeless or partially frameless embodiments). Since the weld 2381changes the electrically conductive topology of the heating element2386, electrodes 2331 are optionally placed at in electrical contactwith the heating element 2386 on its opposite ends (optionally, but notnecessarily, in contact with the weld region 2381 itself).

In some embodiments, vaporization of a portion (for example, a volatileportion) of the drug dose comprises heating by an electrically resistiveheating element (mesh, or other form of resistive heating element) 2306.The resistive heating element optionally comprises a material whichdisplays substantial electrically resistive heating; for example,nichrome (typical resistivity of about 1-1.5 μΩ·m), FeCrAl (typicalresistivity of about 1.45 μΩ·m), stainless steel (typical resistivity ofabout 10-100 m), tungsten (typical resistivity of about 52.8 nΩ·m),and/or cupronickel (typical resistivity of about 19-50 μΩ·m). Accordingto the choice of metal, parameters such as heating element length andwidth, metal thickness, aperture size and/or aperture pattern areadjusted to comprise a total resistance across the resistive heatingelement which is, for example, in the range from about 0.05-1Ω, 0.5-2Ω,0.1-3Ω, 2-4Ω, or within another range having the same, higher, lower,and/or intermediate bounds.

Optionally, during assembly, the resistive heating element 2306 isattached to the housing 2301, in a position overlying the drug dose load2304 on one or more sides. For example, the resistive heating element2306 extends from a dorsal surface 2309A to fold around housing end2311, and extend back along ventral surface 2309B. Optionally, resistiveheating element 2306 extends around chamber 2303 such that a drug doseload 2304 contained within chamber 2303 is enclosed by the heatingelement 2306. In some embodiments, the resistive heating element 2306comprises a plurality of separate panels, for example, panels 2356 and2356A of FIGS. 5C-5D, one on each side of the cartridge 2350.Optionally, the panels are electrically connected, one to the other.Alternatively, each receives separate electrical connections. Apotential advantage of two-sided enclosure of the drug dose load 2304(used in some embodiments) is increased speed and/or uniformity ofvolatilization upon application of a current to the heating element2306. In some embodiments, only one panel 2356 of the enclosure is anelectrically resistive element, and the other panel 2356A is optionallya mesh or other air-permeable structure (for example, a porousstructure) which provides mechanical support.

In some embodiments, electrically resistive heating elements 2356, 2356Aare operated simultaneously. In some embodiments, the resistive heatingelements are operated separately. This is a potential advantage, forexample, to allow separate control and/or release of two differentsubstances, and/or of a single substance in two sequential dosingsequences. For example, a first heating element (panel, for example) isoperated with sufficient energy to vaporize drug substance directlyunderneath it, but for a sufficiently short time or in such a heatingpattern that the heat does not reach all the way through the pallet. Atsome offset in time (optionally overlapping or entirely separate fromthe first heating), a second heating element is operated. Potentially,this is an advantage when two substances having different volatilizationproperties as a function of time or temperature are to be released (forexample, from two different pallet materials). Optionally, the twoheating profiles are adjusted to result in simultaneous vaporization.

Additionally or alternatively, vaporization of two substances isdeliberately offset in time. For example, material comprising aflavoring or masking agent is placed in the pallet near a heatingelement where it is vaporized first, and a second material vaporizedshortly thereafter (or the reverse). This is a potential advantage, forexample, to mask potentially unpleasant tastes, to signal a user as to astatus of vaporization in process, and/or to otherwise modify thesensory experience of inhalation. Optionally, each electrode heatsacross a whole side of the pallet. Alternatively, each heating elementis formed so that vaporization heating occurs only across a portion ofthe pallet, optionally in a different portion for each electrode. Insome embodiments, one heating element is used to “prewarm” a substanceto a threshold below active substance release, and a second heatingelement is activated to achieve release itself. Potentially, prewarmingfollowed by release heating shortens a period of substance releaseand/or increases a concentration upon release. Potentially, this helpsto increase the amount of substance reaching the lungs, and/or to targetrelease to a narrower selected respiratory depth.

In some embodiments, at least one heating element 2306 is embeddedwholly or partially within a drug dose load (pallet) 2304 (also shown,for example, in FIGS. 5G-5H). Optionally, a heating element 2306 isembedded partially or wholly within the frame of a housing 2301. Forexample, the housing 2301 is originally molded with the heating elementin place, and/or the heating element 2306 is pressed into place underhigh temperature at another stage of manufacturing. Optionally aplurality of heating elements 2306 are embedded wholly or partiallywithin a drug dose load (pallet) 2304, with electrical contactsoptionally arranged to allow separate or simultaneous operation.

In some embodiments, resistive heating element 2306 and/or permeableoverlay 2375 comprises a ratio of open (aperture) to closed (mesh orother material) surface area of between about 1:1 (50%) and 1:3 (33%).In some embodiments, the ratio is in the range of about 10%-20%, about20%-40%, about 30%-50%, about 40%-70%, about 60%-80%, about 70%-90%, oranother range of ratios having the same, larger, smaller, and/orintermediate bounds. In some embodiments, the apertures of the mesh arein the range of about 25 μm, 32 μm, 50 μm, 75 μm, 100 μm, 200 μm,300-750 μm, 700-1200 μm, or another larger, smaller, or intermediaterange. Optionally, at least two apertures have different size and/orshape.

FIGS. 5G-5H show another embodiment of a cartridge 2370 comprising anembedded heating element 2376 in a frame 2371. In some embodiments,heating element 2376 comprises a heating section 2378 arranged between aplurality of electrode pads 2377. In the assembled dose cartridge,heating section 2378 extends across or within chamber 2303 and across orthrough a pallet 2304. For example, pallet 2304 is optionally formed bypressing loose material into place around the heating element 2376,embedding it. Optionally, frame 2371 comprises one or more recesses2377A, which receive electrode pads 2377. In some embodiments,additional mechanical support for the pallet is provided by a permeableoverlay 2375, extending over at least one side of the cartridge frame2371. Overlay 2375 optionally comprises a polymer mesh or otherstructure allowing gas flow.

In some embodiments, the heating section 2378 of heating element 2376 isformed as a wire which crosses chamber 2303 one or more times inconnecting to electrode pads 2377. In some embodiments, heating section2378 comprises a mesh, ribbon, or other shape. In some embodiments,heating section 2378 is divided into a plurality of separate parts(branches, layers, or other divisions). In some embodiments, the heatingsection 2378 extends nearby (for example, within 1 mm, within 2 mm, orwithin another larger or smaller distance) substantially all parts ofthe pallet containing the drug substance to be released. This is apotential advantage for obtaining more rapid and/or uniform substancerelease upon heating.

It is to be understood that although electrode contacts 2377 areelectrically separated from one another except as joined by the heatingsection 2378, they need not be placed physically distant from oneanother, depending, for example, on the course(s) run by the heatingsection 2378 itself. Optionally, the electrode contacts are placed onthe same or on different sides of chamber 2303, for example.

In some embodiments, resistive heating element 2306 comprises an etchedresistive foil (for example a foil etched into a continuous ribbon orother shape, and backed by a polymer such as polyimide and/or siliconerubber). Optionally a backed resistive foil is perforated through thebacking to allow airflow during volatilization of the drug dose. In someembodiments, a fuse is added to the resistive foil, for example as anadded component, and/or as a region of ribbon manufactured deliberatelythin, so as to provide a method of destroying the heating element afteruse (by sending an appropriately high current through the heatingelement for a sufficient period of time).

In some embodiments, resistive heating element 2306 is secured to thecartridge housing 2301 by pressing the heating element onto the housing(for example, at housing region 2308) using a temperature high enoughfor the housing to melt and/or soften such that the heating elementbecomes embedded in the material of the housing. This is particularlyappropriate, for example, for use with a housing comprising athermoplastic. Alternatively (for example, if the housing comprises athermoset polymer), cold press joining is used. Additionally oralternatively, the heating element is secured by ultrasonic welding,crimping, gluing, or another method of joining.

In some embodiments, the housing comprises an inert, thermally resistantmaterial. In some embodiments, the housing material used comprises, forexample, a liquid crystal polymer (LCP), polyether ether ketone (PEEK),Ultem, Teflon, Torlon, Amodel, Ryton, Forton, Xydear, Radel, Udel,polypropylene, Propylux, polysulfone, polyether sulfone, acrylic, ABS,nylon, PLA, polybenzimadazole, polycarbonate, polyetherimide,polyethylene, polyphenylene oxide, polyphenylene sulfide, polystyrene,polyvinyl chloride, another thermoplastic, and/or another polymermaterial. In some embodiments, the housing comprises a non-conductiveand/or semiconductive material. In some embodiment, the housingcomprises a conductive material (for example, aluminum), optionallyinsulated electrically from the resistive heating element, for exampleby an insulating layer such as an anodized coating.

A potential advantage of LCP and/or PEEK is good resistance totemperature higher than a temperature needed to vaporize a substanceheld in the cartridge. In some embodiments, bonding of heating elementand housing occurs at a temperature of about 280° C. (or anothertemperature high enough to melt and/or soften LCP or PEEK). LCP and PEEKprovide the potential advantage of good thermal stability at lowertemperatures, for example, at a vaporization temperature of about 230°C.

In some embodiments, a conductive or semi-conductive housing material isused, optionally provided with a non-conductive separator. For example,the housing material comprises anodized aluminum.

A potential advantage of providing a heating element such as anelectrically resistive heating element 2306 for each individual dosecartridge is to provide uniformity of performance between uses.Potentially, a portion of the heated compounds with which a heatingelement comes into contact remain stuck to the heating element aftercool down. This buildup has the potential to affect vaporizationperformance. Remote heating (by radiation and/or indirect conductance,for example) potentially produces a system having relatively highthermal inertia (needing greater heating power) compared to directconductive heating by a contact electrode; the problem of contactelectrode contamination is removed by designing it for single use. Alowered requirement for heating potentially increases safety and/ordevice longevity. Potentially, a lowered requirement for heating alsolowers demands on power delivery, allowing embodiments with increasedportability, greater charge life, and/or lowered expense (for example,for systems having battery-powered heating elements).

In some embodiments, a cartridge 2300 comprises a locking member for usein cartridge transport. The locking member comprises, for example, alatch mandible 2302. The locking allows engagement by one or morematching members of a vaporizer device transport mechanism, for securingand/or movement of the cartridge. Cartridge movement and/or securingagainst unwanted movement may occur during the cartridge life cycle, forexample: when the cartridge is placed into a queue of cartridgescomprising a plurality of cartridges arranged for use, when thecartridge is advanced in the queue, when a cartridge is selected foruse, when a cartridge is moved into position for use, when a cartridgeis actually used, and/or when a cartridge is discarded, or,alternatively, moved to a “used” position in the cartridge queue.

In some embodiments, a dose cartridge 2300 comprises a button cartridge,wherein the drug dose is substantially encapsulated by a porous,flattened capsule which optionally comprises the material of the heatingelement surrounding or nearly surrounding the drug dose. The porouscapsule is, for example, round, square, rectangular, oval, or anothershape. Optionally, transport of a button cartridge comprises, forexample, pressing, pulling, and/or clamping the surfaces of the capsule,and/or operation of magnets (where the button cartridge comprisesmagnetically susceptible material). In some embodiments, at least oneportion of a dose cartridge 2300 (a button cartridge, or any other dosecartridge) is sufficiently thick alongside one or more edges of the drugdose pallet itself to avoid or reduce wastage and/or uneven drugsubstance release from the volume of the pallet. For example, a sidesupport member of the dose cartridge is large enough to allow a stablehold, while substantially the entire drug dose pallet is heated torelease drug substance which can freely diffuse into a stream ofairflow.

In some embodiments, a dose cartridge 2300 comprises a central supportmember surrounded by drug dose substance, which bridges between twofaces of the drug dose to interconnect a plurality of air-porous palletface supports. For example, a dose cartridge comprises a spindle or reelframe shape, with the substance of the drug dose pallet packed aroundthe core of the spindle. Optionally, transport and/or holding of thedose cartridge comprises manipulation of the core of the spindle, whichis optionally hollow, and the hollow is optionally open on at least oneface of the dose cartridge.

Granulation of Botanical Substance

Reference is now made to FIG. 1, which is a schematic flowchart of amethod of preparing a granulated botanical substance for use in dosepackaging with an inhaler device, according to some embodiments.Reference is also now made to FIG. 3, which is a schematic view of abotanical substance grinding apparatus 2200, according to someembodiments. Reference is also made to FIG. 4, which is a schematic viewof the grinding plate 2220 of a botanical substance grinding head 2204,according to some embodiments.

In some embodiments, formation of a drug dose load 2304 comprisesprocessing through a granulated intermediate form 2214 of an organicsubstance (for example, a botanical substance 2212). Granulationoptionally allows control of drug dose load 2304 shape, structure,and/or density. A potential advantage of granulation is to increase thegrain surface area exposed to gas (for example, heated gas) passingthrough a permeable drug dose load 2304. Potentially, granulation allowsincreased homogenization of the drug dose load, for increasedreproducibility of dosage amount.

At block 2002, in some embodiments, the flowchart begins, and abotanical substance for use in formulating a dosage is received. In someembodiments, the botanical substance comprises cannabis, optionallycannabis flowers in particular. In some embodiments, a botanicalsubstance received for use in formulating dosage comprises any whole orportion of a plant, including for example one or more of: Cannabissativa, Cannabis indica, Cannabis ruderalis, Acacia spp., Amanitamuscaria, Yage, Atropa belladonna, Areca catechu, Brugmansia spp.,Brunfelsia latifolia, Desmanthus illinoensis, Banisteriopsis caapi,Trichocereus spp., Theobroma cacao, Capsicum spp., Cestrum spp.,Erythroxylum coca, Solenostemon scutellarioides, Arundo donax, Coffeaarabica, Datura spp., Desfontainia spp., Diplopterys cabrerana, Ephedrasinica, Claviceps purpurea, Paullinia cupana, Argyreia nervosa,Hyoscyamus niger, Tabernanthe iboga, Lagochilus inebriens, Justiciapectoralis, Sceletium tortuosum, Piper methysticum, Catha edulis,Mitragyna speciosa, Leonotis leonurus, Nymphaea spp., Nelumbo spp.,Sophora secundiflora, Mucuna pruriens, Mandragora officinarum, Mimosatenuiflora, Ipomoea violacea, Psilocybe spp., Panaeolus spp., Myristicafragrans, Turbina corymbosa, Passiflora incarnata, Lophophorawilliamsii, Phalaris spp., Duboisia hopwoodii, Papaver somniferum,Psychotria viridis, spp., Salvia divinorum, Combretum quadrangulare,Trichocereus pachanoi, Heimia salicifolia, Stipa robusta, Solandra spp.,Hypericum perforatum, Peganum harmala, Tabernaemontana spp., Camelliasinensis, Nicotiana tabacum, Nicotiana rustica, Virola theidora,Voacanga africana, Lactuca virosa, Artemisia absinthium, Rexparaguariensis, Anadenanthera spp., Corynanthe yohimbe, Caleazacatechichi, Coffea spp. (Rubiaceae), Sapindaceae spp., Camellia spp.,Malvaceae spp., Aquifoliaceae spp., Hoodia spp. Chamomilla recutita,Passiflora incarnate, Camellia sinensis, Mentha piperita, Menthaspicata, Rubus idaeus, Eucalyptus globulus, Lavandula officinalis,Thymus vulgaris, Melissa officinalis, Tobacco, Aloe Vera, Angelica,Anise, Ayahuasca (Banisteriopsis caapi), Barberry, Black Horehound, BlueLotus, Burdock, Camomille/Chamomile, Caraway, Cat's Claw, Clove,Comfrey, Corn Silk, Couch Grass, Damiana, Damiana, Dandelion, Ephedra,Eucalyptus, Evening Primrose, Fennel, Feverfew, Fringe Tree, Garlic,Ginger, Ginkgo, Ginseng, Goldenrod, Goldenseal, Gotu Kola, Green Tea,Guarana, Hawthorn, Hops, Horsetail, Hyssop, Kola Nut, Kratom, Lavender,Lemon Balm, Licorice, Lion's Tail (Wild Dagga), Maca Root, Marshmallow,Meadowsweet, Milk Thistle, Motherwort, Passion Flower, Passionflower,Peppermint, Prickly Poppy, Purslane, Raspberry Leaf, Red Poppy, Sage,Saw Palmetto, Sida Cordifolia, Sinicuichi (Mayan Sun Opener), Spearmint,Sweet Flag, Syrian Rue (Peganum harmala), Thyme, Turmeric, Valerian,Wild Yam, Wormwood, Yarrow, Yerba Mate, and/or Yohimbe. The dosingbotanical substance optionally includes any combination of plantmaterial from this list, and/or other plant material.

Grinding of the botanical substance is described with respect to the useof a grinder 2200, for purposes of illustration. It is to be understoodthat in some embodiments, another grinders capable of producingparticles of sufficiently small size and uniformity for forming into adrug dose load are used. Optionally, the grinder is capable of producingthe particles without significantly damaging the macroscopic plantstructure of the botanical substance, for example without burstingand/or breaking the trichomes of a cannabis plant.

At block 2004, in some embodiments, the botanical substance 2212 isplaced in a sieving chamber. The sieving chamber comprises a mesh orother perforated surface 2206, the perforations being, for example,about 500 μm in pore size. Optionally, the pore size is, for example,about 250-400 μm, 350-600 μm, 500-700 μm, 650-900 μm, 800-1000 μm, oranother range of pore sizes having the same, larger, smaller, and/orintermediate bounds.

At blocks 2006, and 2008 in some embodiments, the sieve is placed in agrinder body 2202, optionally together with a moisture absorptionsubstance 2208. Moisture absorption substance 2208 helps to keep controlthe moisture content of the granules 2214, for example, to obtain aconsistent range of granulated material characteristics includingself-adhesion, and relative weight-percent dose concentration.Potentially, the moisture absorption substance 2208 helps to preventfree-frost formation during the cryogenic stages of the grindingprocess.

At block 2010, in some embodiments, the grinder 2200 is cooled.Optionally, the cooling is using a cryogenic fluid 2210 to a temperaturein the range, for example, of −50° C. to −180°. Optionally, thecryogenic fluid 2210 is liquid nitrogen, or another cryogenic fluidappropriate to the target temperature range.

At block 2012, in some embodiments, a grinding head 2204 is lowered tothe level of the botanical substance while spinning, and graduallylowered further as particles are further ground. An example of agrinding head grinding plate 2220 is shown in FIG. 4, comprising rigidprotrusions 2216 (which act to break up the frozen botanical substancewhen they press against it). Optionally, fine brushes 2218 act to spreadparticles of ground material over the plate, such that particles whichhave been ground to a sufficient degree of fineness fall through thesieving pores into a receiving chamber 2213.

At blocks 2014 and 2016, in some embodiments, the grinder is broughtback to ambient temperature, unsealed, and the sieved granulate removedfrom the receiving chamber 2213. The granulate is homogenized, forexample, by use of a V-mixer, circular mixer, or other homogenizingprocess.

Packaging of a Botanical Substance to a Dose Cartridge

Reference is now made to FIG. 2, which is a schematic flowchart of amethod of packaging a botanical substance to a dose cartridge for usewith an inhaler device, according to some embodiments.

In some embodiments, material for forming a drug dose (for example,granulated material, as described in relation to FIG. 1) is incorporatedinto a dose cartridge 2300 by a process of pressing a metered amount ofthe material into a receiving chamber 2303 in the cartridge. Optionally,the pressing is to a degree which provides a chosen degree of thinness(thinner packages potentially heat more quickly and/or evenly), and/or achosen degree of density (a package should not be too dense to allow thepassage of airflow during vaporization).

At block 2102, in some embodiments, a first branch of the flowchartbegins for the cartridge packages of botanical granulate. In someembodiments, the humidity and temperature of the packaging area arecontrolled, for example, to a temperature of 20° C. and a humidity of30%. It should be understood that other environmental conditions areused in some embodiments (for example, the temperature can potentiallybe within about ±5° C. of 20° C.; the humidity can be within about ±10%of 30%). The variables of temperature and humidity, as selected, may beset to consistent levels in order to maintain consistent dosing. Also,conditions selected should be such that the botanical granulate neitherbecomes too dry to pack well, nor too wet to distribute evenly.

A measured amount of botanical granulate is placed in an open receivingchamber 2303 of a dose cartridge housing 2301. Optionally, one side ofreceiving chamber 2303 is closed by an electrically resistive heatingelement 2306 which is optionally a mesh, or another heating elementwhich is perforated to permit the passage of air through the granulate,while retaining the granulate in place. Alternatively, the receivingchamber 2303 is placed against a firm flat surface from which thegranulate is easily removed (for example, a relatively low frictionpolymer surface such as PTFE). Optionally, receiving chamber 2303comprises a thin, heat-conductive bottom wall which is perforated topermit the passage of air through the granulate, while retaining thegranulate in place.

Optionally, receiving chamber 2303 comprises a reticular formation (anet, mesh, or other structure), which serves as an anchor for materialduring pressing (for example, at block 2106). In some embodiments, areticular formation or a permeable retaining element which is optionallynot itself a heating element is provided on the exterior of the dosecartridge, serving to provide mechanical support for a pallet in thereceiving chamber 2303, while also permitting the passage of air.

The amount of measured granulate is optionally chosen according to thepotency, concentration, and/or volatility of the vaporizing fraction.When cannabis granulate is used, for example, the measured amount isoptionally 15 mg, or another value in the range of 10-20 mg. Choice ofamount optionally depends, for example, on plant variety, growingconditions, and/or assay results of a botanical substance available forpackaging. In some embodiments, the measured amount is within the range,for example, of 1-20 mg, 10-40 mg, 25-75 mg, 50-100 mg, or withinanother range of amounts having the same, intermediate, larger, orsmaller bounds. In some embodiments, for example, if the required dosageis too small to fill the substance receiving chamber, a filler substanceis optionally added; for example, a portion of an inert (lackingvolatile drug activity) botanical substance. Optionally, the filler isuniformly mixed with the required dosage.

At block 2104, in some embodiments, the granulate is distributed withinthe receiving chamber 2303. In some embodiments, distribution comprisesleveling the housing 2301 (placing it horizontally flat), and shakingthe housing with the granulate inside vertically (for example, byvibrating the cartridge 2300 and/or the surface that the cartridgehousing 2301 rests on), until a leveled plain of granulated substance isformed within the chamber 2303. In some embodiments, the vibrating iswith an amplitude in the range of about 0.1-1.2 mm; for example 0.5 mm.The frequency of vibration is, for example, in the range of about 20-300Hz (such as 30 Hz, 45 Hz, 60 Hz, 75 Hz, or another higher, lower, orintermediate frequency). Duration of shaking is, for example, chosenfrom within the range of 100-1100 msec (such as about 300 msec, 400msec, 500 msec, 800 msec, or another longer, shorter, or intermediatetime). Optionally, the chamber is secured before vibration, to preventgranulate from escaping the chamber from underneath.

At block 2106, in some embodiments, granulate is compressed by the useof a press. Optionally, the press lowers vertically down upon thedistributed granulate, forming it into a small pallet 2304 of compressedgranules. Compression is to a thickness which is, for example, in therange of 10-50% of the pre-compression thickness of the distributedgranulate mass. Compression is, for example, to about 15%, 20%, 30%,40%, or another larger, smaller, or intermediate value of theuncompressed thickness of the distributed granulate mass. In someembodiments, the granulate is compressed to a pallet of thickness withina range of between about 200-1500 μm, or thickness within another rangehaving the same, larger, smaller and/or intermediate bounds.

At block 2108, in some embodiments, the press is removed. In someembodiments, the press is removed by sliding horizontally across thesurface of the cartridge housing 2301. Potentially, this allowsgranulate residue which may stick to the press tool to be scraped off atthe edge of the receiving chamber 2303. Optionally, granulate which hasbeen compressed into the chamber is fixed thereby, and remains in placeduring additional handling to finish the cartridge preparation.

Other methods of filling the drug dose receiving chamber are alsocontemplated as separate embodiments as will be apparent below.

For example, at block 2114, in some embodiments, an alternative branchof the flowchart begins. As an alternative to the formation by granulatepressing of drug dose load 2304 for a cartridge 2304, a portion of abotanical substance tape is trimmed to the size of a substance receivingchamber 2303 of a dose cartridge housing 2300. In some embodiments, thebotanical substance tape is formed, for example as described inInternational Patent Application Publication No. 2012/085919. At block2116, in some embodiments, the trimmed tape portion is inserted to thesubstance receiving chamber 2303.

Also for example, at block 2118, in some embodiments, anotheralternative branch of the flowchart begins. Optionally, a materialcontaining a drug substance from which a drug dose is formed isavailable as fluid and/or gelatinous extract, fine suspension, and/orsolution. The drug dose receiving chamber then optionally comprises anair-permeable portion (for example, foam, sponge, felt or other fibermatrix, and/or another porous structure) which absorbs the drugsubstance containing material to fix it into place.

At block 2110, in some embodiments, any one of the three branchescontinues. Resistive heating element 2306 (a mesh, for example, oranother heating element such as an etched foil) is attached to thecartridge housing 2301, for example by pressing against the housing andheating until the two parts are fused by softening and/or melting of thehousing material. Attachment is optionally on one or both sides of thesubstance receiving chamber 2303. In some embodiments, a heating elementin a “U” shape wraps around the cartridge housing 2301 to enclose thechamber 2303 on two sides, for example, within the hollow of the “U”.

Dose Cartridge Carousel and Vaporizing Device

Reference is now made to FIGS. 6A-6E, which schematically illustrate acarousel-type dose delivery system 2340 for use with an inhaler device,according to some embodiments.

In some embodiments, the dose delivery system 2340 comprises a carousel2322 holding a plurality of dose cartridges 2300 encased by an enclosure2324, and an inhaler device 2321 comprising a dose puller 2314 and aclamping chamber 2320. Carousel enclosure 2324 and the inhaler device2321 are attached to one another; the carousel 2322 revolves to presentcartridges to the inhaler device 2321 in the order of their positionswithin the carousel, or in another order, as selected by operation ofthe carousel 2322. Optionally, the carousel enclosure 2324 (and itscontents) are exchangeable for a new enclosure assembly, for examplewhen dosages are exhausted, and/or to change the dosing composition.

The number of dosage cartridges carried by an enclosure is, for example,about 100. Optionally, the number of cartridges is another number withinthe range of 10-200 (for example, 10, 40, 80, 120, 180, or 200), oranother larger or smaller number. In some embodiments, carousel diameteris, for example, within the range of about 7-10 cm, or another larger orsmaller diameter, according, for example, to the number and size ofcartridges to be accommodated. Optionally, carousel 2322 comprisesidentical doses or a plurality of different doses (for example,different amounts, concentrations, and/or substance compositions). It isto be understood that a carousel is not the only form of cartridgestorage device (magazine) which is usable with dose cartridges. Forexample, the dose cartridges can be stored within a linear-type magazinestorage system (for example, as described in relation to FIGS. 11A-11C).A potential advantage of a carousel over a linear-type magazine isrotationally selectable access during loading and/or unloading to dosingpositions; for example, to effect a dosing regimen (namely, to providethe user with a defined sequence of inhalations from dose cartridgeseach having a different substance and/or a different amount of asubstance and/or different substance ratios) and/or to adjust a dosingregimen after the magazine was already loaded with dose cartridges. Insome embodiments, a carousel-type magazine reduces a longest dimensionrelative to a linear-type magazine, for a similar count of cartridgescontained.

In an example of an operation cycle, dose puller 2314 is actuated toextend from the inhaler device into the carousel enclosure 2324, whereit attaches to a dose cartridge 2300, for example, by means of latchmandibles 2302. In some embodiments, the dose puller 2314 “snaps” intoplace within the latch mandibles 2302. In some embodiments, the dosepuller 2314 comprises two parts which move laterally past opposite sidesof, and then close together within the space defined by the mandibles2302 (potentially applying a lower force to the mandibles 2302 and/orcartridge 2300 than a snap-inserting method). A further action draws theactuator back into the inhaler device, and the attached cartridge 2300along with it. The drug dose load 2304 of the cartridge 2300 is drawnthereby into communication with an air intake 2312. It is to beunderstood that a dose puller potentially operates in a mode other thantransport by an actuated arm: for example as a dose “pusher”(comprising, for example a spring loaded member in the carousel volumeitself), and/or a magnet (in a pulling mode) or magnets (in a pushing orpulling mode).

In some embodiments, clamping members 2310A and 2310B close on thecartridge, bringing electrodes into place for heating the drug dose forvaporization of the volatile substances within it.

Reference is now made to FIGS. 11A-11C, which schematically illustrate alinear-type dose cartridge magazine 1100 for use with an inhaler device,according to some embodiments. FIG. 11A shows an external view, the viewof FIG. 11B shows magazine housing 1110 as partially transparent, andFIG. 11B shows the magazine 1100 in cross-section.

In some embodiments, a linear-type dose cartridge magazine 1100comprises a housing 1110 having at least one cartridge access slot 1105,through which a dose cartridge 2300 is dispensed; for example, bygripping latch mandibles 2302 from a position at, protruding, or withinaccess slot 1105. Optionally, the dose cartridges 2300 within thehousing are transported by a spring, piston, screw, or other mechanismin one or both directions within the housing 1110. In some embodiments,cartridge transport is driven in whole or part by actions of withdrawingand/or replacing a cartridge. For example, in some embodiments, acartridge 2300 is withdrawn from a first slot 1105, causing the nextunused cartridge to be advanced into position for selection. In someembodiments, a cartridge 2300 is returned to a second slot (optionally,the same slot 1105, with an additional mechanism to control advancing),pushing a stack of used cartridges 2300 (e.g. a spring-loaded stack)deeper into a used-cartridge receptacle storage area. This provides apotential advantage for simplicity, security, and/or cost. In someembodiments, cartridges are optionally transported within housing 1110under motorized control (for example, pushed by one or more plates incontact with a motorized lead screw). A potential advantage of motorizedcontrol is to allow non-sequential and/or non-predetermined access todose cartridges—for example, to allow selection of a dose cartridgeaccording to a pre-defined regimen, and/or a dynamically defined dosecartridge regimen.

Reference is now made to FIGS. 7A-7B, which schematically illustrate aclamping chamber 2320 for heating and delivery of vaporized substancefrom a dose cartridge 2300, according to some embodiments. Reference isalso made to FIG. 7C, which schematically illustrates a cross section ofclamping chamber 2320 clamping a cartridge 2300, according to someembodiments.

In some embodiments, cartridge 2300 is transported into the clampingchamber 2320, for example by movement of dose puller 2314 while engagedwith latch mandible 2302.

In some embodiments, clamping chamber 2320 comprises two clampingmembers 2310A, 2310B, which engage cartridge 2300 during dosevaporization. In some embodiments, each clamp 2310A, 2310B carries acorresponding electrode 2330A, 2330B, which is positioned to come intopressing contact with a resistive heating element 2306 or other heatingelement which the cartridge 2300 carries. Electrodes 2330A, 2330B are inturn in electrical contact with a power supply for supplying electricalcurrent. Heating is delivered, in some embodiments, by switching currentthrough the electrodes 2330A, 2330B, via the heating element 2306.Optionally, the electrodes 2330A, 2330B are positioned to contact theresistive heating element 2306 such that current follows pathwaysthrough the resistive heating element 2306 which extend oversubstantially all of at least one side (two sides, in the illustratedexample) of the drug dose load, such that heat may be evenly distributedover and conducted to the surface of load 2304.

In some embodiments, air 2315A flow passes through intake 2312, throughthe heated drug dose load 2304, during which passage the air 2315Abecomes drug substance laden air 2315B, and out of the output aperture2312B. Optionally, the output aperture 2312B is in fluid communicationwith a tube which is routed for delivery of the vaporized substances toa user. Optionally, the clamping members 2310A, 2310B comprise portionsof the intake 2312 and output 2312B. Potentially, this allows the clampmembers 2310A, 2310B to alternately open for receiving a cartridge 2300,and close to seal an airway passage around the cartridge 2300, so thatvaporized substance is kept confined to a defined passageway. In someembodiments, the clamp members 2310A, 2310B comprise air seals 2313,which close around the cartridge 2300 so as to substantially preventsubstance vaporization and/or airflow transfer except along the pathwaywhich conducts air to the user. Optionally, air seals 2313 comprise anelastically deformable material such as a polymer rubber. In someembodiments, electrodes 2330A, 2330B are also protected from the airflowby air seals 2313, optionally including any vaporizing portions of thepallet 2304. A potential advantage of closing the electrodes away fromvaporized material is to reduces and/or prevent the electrodes frombecoming contaminated due to repeated use.

In some embodiments, the electrodes 2330A, 2330B are block shaped (forexample, as shown in FIGS. 7A-7B), providing a substantially planarcontact surface with the heating element. In some embodiments, anotherelectrode contact surface shape is used. In particular, a blade-likecontact surface (long and thin, for example, with the thinner dimensionbeing less than 0.5 mm, 0.3 mm, 0.1 mm, or another greater, smaller, orintermediate size), or a curved contact surface (for example, having anat least partially circular, elliptical, or other curved cross-section)is provided. Optionally, using such a shape reduces contact surfacearea, and concentrates clamping force, resulting in increased clampingpressure. This in turn potentially increases reproducibility ofelectrical contact and/or reduces electrical resistance (and energylosses) at the region of electrical contact with the cartridge. Forexample, the inventors have found that, in some embodiments, anelectrode/heating element contact force of about 500 N, used with acurved contact surface electrode design (and/or, for example, a pressureof about 70 N/mm²), reduces electrical contact resistance tosubstantially zero (for example, less than 1% of total circuitresistance). In some embodiments, power loss due to resistance acrossthe electrical contact is less than, for example, about 1%. Inparticular, a curved (for example, cylindrical) electrode contactsurface provides a potential advantage for reproducible contact bycombining a low contact surface with robust mechanical support behindthe surface.

After dose delivery, ejection of the cartridge comprises disengagementof dose puller 2314 from latch mandible 2302; for example, by displacingone of the two parts while restraining the other from following, and/orby deforming one of the two parts. For example, puller 2314 is furtherretracted, while cartridge 2300 is prevented from following by arestriction in the size of the slot through which it moves. In someembodiments, disengagement is followed by ejection: for example, thecartridge falls out of its slot, is pushed by a returning action of thedose puller 2314, and/or is otherwise transported out of the devicealtogether. In some embodiments, the cartridge is returned to carousel2322 as a used dose (into the same, or another available slot differentfrom the one it was retrieved from). Optionally, this is performedshortly or immediately at the end of use. Alternatively, the cartridgeis ejected in the framework of a next use of the device, in which casethe carousel also advances to present the next cartridge to be used.

In some embodiments, access to doses loaded in the carousel issequentially in the order of their positions within the carousel. Insome embodiments, dosage order is pre-determined but variable; forexample, dosages of different amounts for administration throughout aperiod of time are arranged in that order when the carousel is loaded.In some embodiments, carousel movement (advancing) is substantiallyaccording to a sequence of actions which are mechanically coupled to thedose pulling and/or dose returning actions. In some embodiments,carousel movement (or dose cartridge selection for another magazinetype, such as a linear-type magazine) is under the control of acontroller, for example, a microprocessor-controlled stepper motor orother advancing mechanism.

Optionally, the controller tracks which dosage is in which cartridgeslot, and/or its status. Optionally, the controller automatically and/orupon command selects an appropriate cartridge, and advances it into useposition by as many steps as needed to make it available for pulling.Optionally, this selection allows out-of-order access to cartridges inthe carousel (or other magazine configuration). Optionally the carouselor other magazine advances as a result of a user actuating the device.In some embodiments, there is more than one use position (for example,there are two or more clamping chambers) and the controller isconfigured to select a combination of cartridges from the magazine fromany specified location within the magazine.

In some embodiments, a controller selects a dose according to a progressof a dosing regimen. For example, if a first drug dose is determined tohave been only partially administered (for example, due to a detectedproblem during inhalation), the controller optionally selects a secondpartial dose, for additional administration. Additionally oralternatively, the strength of a drug dose is selected by a controllerbased on a time elapsed since a previous dose was administered. Thispotentially allows repeated dosing by a user, while maintaining controlwhich potentially prevents overdosing.

In some embodiments, a controller is configured to present dosecartridges 2300 from a magazine or other cartridge holder for aplurality of inhalations to be taken sequentially as part of a singledosing, for example in a single session, or a plurality of sessionsseparate by brief intervals. Optionally, the device advises the userbefore the use on the number of inhalations to be performed and the usersimply takes the number of inhalations with the device as instructed,while the device automatically selects the cartridges in accordance witha certain regimen. In some embodiments, the user is prompted (forexample, by an audible or visible stimulus) as long as there areadditional doses remaining in the current inhalation series. Optionally,the controller replaces dose cartridges automatically as they are used.Alternatively, the user is prompted to perform an action for dosecartridge replacement (for example, moving the mouthpiece or pressing abutton).

Optionally, the device is configured to enforce a minimum intervalbetween inhalations. This is a potential advantage to reduce thelikelihood that a user will perform one or more of the later inhalationsimproperly. For example, a minimal time period of about 2-5 minutes isoptionally imposed by the device between each inhalation and/or doseexchange. Additionally or alternatively, a rapid sequence of inhalations(e.g. separated by no more than a few seconds) is performed as fast asis convenient to the user (i.e. without an imposed minimal interval).This provides the potential advantage of being less time consuming intotal. Optionally, one or more minimal interval periods are imposed whena sequence of inhalations is long enough to warrant a mandatory rest ofthe user and prevent shortness of breath.

Detachable Vaporizing Device

Reference is now made to FIGS. 8A-8B, which schematically illustrate adosage delivery device for loading from a carousel, and separable fromthe carousel for delivery of the dose itself, according to someembodiments.

In some embodiments, functions performed by clamping chamber assembly2320 are performed by separable parts, such that aclamping/heating/administration subassembly is separable from portionsof a dose storage pulling and transport subassembly, at least for doseadministration to a user. In some embodiments, theclamping/heating/administration assembly 2400 comprises a substantiallycylindrical body (for example, cigarette, cigarillo, cigar, and/or penshaped), which inserts into a receptacle of the dose pulling andtransport assembly. The assembly 2400 comprises a slider mechanism 2410or other structure which is engaged by the transport assembly, and/or isactivated by manual or other external operation.

Optionally, slider mechanism 2410 slides out of the intake end 2440 ofthe assembly 2400 to engage a cartridge 2300 with engaging part 2415, asdescribed, for example, in relation to dose puller 2314. Optionally, thecartridge 2300 (formed, for example, with a long and narrow drug doseload 2404) is pulled into the clamping/heating assembly. Theclamping/heating assembly optionally comprises electrodes 2430 which areloaded with spring members 2407, or another means, for pressing againstresistive heating element 2306 to provide electrical contact thereto.Optionally, power for heating is supplied by a battery 2413 connected toelectrodes 2430 via wires 2414. Optionally, the battery 2413 isrechargeable, for example, the battery 2413 recharges from a supplyprovided by the main body assembled together with the carousel.Optionally, heating begins upon operation of a control (such as abutton), and/or is subject to one or more automatic activation,modulation, and/or interlock controls, such as heating upon sensing of achange in pressure, and/or air shunt opening to control speed and/oramount of dose delivery. During dose delivery, air is drawn through thebody 2420 (for example, orally), by applying suction to end 2450. Airdrawn into intake end 2440 is forced by baffles/conduits 2401, 2408 topass through the heated drug dose load 2404, carrying vaporized drugsubstance to end 2450.

A potential advantage of the separable design is to reduce the effortrequired by a user to manage the dosing device at the time of doseadministration. Another potential advantage is to separate the functionsof dosage selection, management, and control from the dosing itself.There is a potential positive psychological effect due the separation ofthe dosing act, which approximates that of a normal e-cigarette, fromthe more clinical aspects of dosage control.

In some embodiments, a removable cartridge comprises a plurality ofseparately heatable regions; for example, material is loaded intodifferent apertures, and/or an aperture which is crossed by a pluralityof separately addressable heating elements. Optionally, the differentloads comprise different substances. For example, a cannabis load isoptionally followed by one or more tobacco loads, and/or by loads ofcannabis that have a different, or even no, THC content.

In some embodiments, analog and/or digital circuit logic is used tocontrol which heating element region receives current. For example, eachheating element is optionally deliberately “burned” (by fuse breaking,for example) after use. A suitably arranged sensing circuit detects afirst unused dosing region, and selects it for the next activation.

A potential advantage of this is to allow a dosage to be spread overmultiple inhalations. Another potential advantage is to allow a dosagefor one purpose (for example, a medicinal purpose) to be combined withdosages for another purpose (for example, an alternative medicinalpurpose, or to allow additional inhalations for the purpose ofenjoyment). Another potential advantage is to allow the use of multipledose types (for example, different flavors) for the sake of givingvariety to the user's experience.

Reference is now made to FIG. 9, which schematically illustrates aninterlock-protected dose dispensing device 2500, together with aremovable dose administration assembly 2400, according to someembodiments.

In some embodiments, dispensing device 2500 comprises a plurality ofreceiving apertures 2501, 2502 for the administration assembly 2400. Insome embodiments, aperture 2501 is an aperture from which an unused dosecartridge 2300C, 2300A is retrieved into administration assembly 2400.In some embodiments, after a dose cartridge 2300A is extracted from thedispensing device 2500, the next dose cartridge 2300C does not advanceinto position until the conditions enforced by an interlock device aremet. In some embodiments, operation of the interlock device comprisesinserting administration assembly 2500 into aperture 2502. Optionally,insertion triggers (for example, by mechanical and/orcontroller-actuated operation) the movement of the carousel such that adose cartridge 2300C is moved into position. In some embodiments,insertion (optionally insertion and removal) of the administrationassembly 2400 extracts cartridge 2300A, which now occupies the formerposition of used cartridge 2300B. Potentially, this interlock mechanismhelps to ensure that only one dose at a time is removed from thedispensing device 2500. In some embodiment, advancing of the carouseldoes not occur unless a cartridge 2300A is sensed within theadministration assembly 2400 upon insertion into aperture 2502. In someembodiments, cartridge 2300A is inserted into administration assembly2400 such that it cannot be removed without destruction of the cartridge2300A and/or the administration assembly 2400.

Plurality of Potentially Simultaneous Doses

Reference is now made to FIG. 10, which schematically illustrates acarousel arranged for potentially simultaneous administration ofsubstances from a plurality of dose cartridges held within two separatecarousel magazines, according to some embodiments.

In some embodiments, a dispensing device 1000 comprises a plurality ofmagazines, shown here as carousel magazines 1010, 1020; each operating,for example, as described in relation to the carousel of FIGS. 6A-6E. Insome embodiments, the magazines 1010, 1020 are stacked, and thecartridge holding chambers 1012, 1022 are arranged to share a commonconduit, or two at least partially parallel conduits for extractionairflow. Magazines 1010, 1020 are optionally housed in a common housing1002 (shown transparent to reveal interior details), or provided withseparate housings.

In some embodiments, operation of the device comprises removal of afirst dose cartridge 2300C from the first magazine 1010, and a seconddose cartridge 2300D from the second magazine 1020. The dose cartridgesare positioned one adjacent the other in a shared clamping chamber 1001(optionally, two separately actuatable clamping chambers are provided).Unladen air 1005 flows via the dose cartridges 2300C, 2300D; laden air1007 exits them bearing at least one drug substance. The applied heatingprofile (comprising time, temperature, heating rate and/or onset, forexample) is optionally identical in the two dose cartridges. Optionally,the applied heating profiles are controlled separately, thus optionallyreleasing the drug substance(s) at different times, and/or releasingdifferent drug substance compositions and/or amounts).

Optionally, airflow is estimated and controlled for both dose cartridges2300C, 2300D in unison. Optionally, only one dose cartridge comprises adrug substance, and a second, inert cartridge occupies the other dosecartridge position. An inert cartridge is, for example, a cartridge thatdoes not comprise a substance (e.g., comprises an inert pallet).Optionally an inert cartridge has similar airflow properties to those ofa dose cartridge it is used with. As an alternative option, the inertcartridge entirely blocks airflow. Optionally, a used cartridge is usedas an inert cartridge.

In some embodiments, the inert cartridge is included in a normalposition of the magazine. Optionally, the inert cartridge is stored inthe device at another accessible location. Optionally the empty positionis blocked, for example by a protrusion from a wall.

In some embodiments, an inert cartridge (for example, a blockercartridge or partition) is present in the dose cartridge magazinepositions by default (for example, placed during manufacture of themagazine, before drug loading). When moving a dose cartridge intoposition during drug loading, the inert cartridge is optionally removedand replaced by the dose cartridge as part of loading. Where no dosecartridge is loaded, the partition optionally remains. Once a used dosecartridge is discarded, the inert cartridge optionally returns toposition, for example by a spring mechanism.

Reference is now made to FIG. 12, which schematically illustrates acarousel 1210 arranged in an inhaler 1200 for simultaneousadministration of substances from a plurality of dose cartridge clampingchambers 1220, 1230 in a corresponding plurality of extraction airflowconduits 1222, 1232, according to some embodiments.

In some embodiments, a plurality of separate extraction airflow conduits1222, 1232 are provided, each comprising a dose cartridge clampingchamber 1220, 1230. Optionally, dose cartridges 2300C, 2300D are drawnfrom a single carousel magazine 1210 or other cartridge magazine.Alternatively, a plurality of magazines is provided. Cartridge drawingis optionally simultaneous, sequential and/or separately operatedaltogether, and optionally while the cartridge magazine(s) remain in asingle position, or with movement of the magazine 1210 (e.g. rotation)between draws.

In some embodiments, flow through the extraction conduits 1222, 1232 isat least partially regulated by providing a draw conduit 1215 in flowcommunication with the extraction conduits 1222, 1232. The total flow ofair 1209 through the device due to inhalation from a mouthpiece 1202 isoptionally divided among all conduits (for example by the sizing and/orsize adjustment of conduit diameters and/or valves), such that theportion of airflow through each extraction conduit 1222, 1232 isadjusted to be within a targeted extraction airflow profile. Remainingairflow is optionally directed through the draw conduit 1215.Optionally, the extraction conduits are operated separately (forexample, only one is operated, or both are operated in sequence).

Optionally, sensors 1240 providing data (e.g. airflow and/or temperaturedata indicative of airflow and/or temperature at the dose cartridgesduring operation) for control are optionally positioned near or via oneor more of the dose cartridges 2300C, 2300D. Control optionallycomprises adjustment of airflow (for example, by adjustment of a valveor aperture position) such that both dose cartridges 2300C, 2300Dsimultaneously experience airflow 1205, 1207 within a given range.Alternatively, adjustment is such that a part of the airflow sequence iscontrolled with respect to a first dose cartridge position 1220, whileanother part is controlled according to second position 1230.Optionally, in some sessions, only one of clamping chambers 1220, 1230is used.

In some embodiments, a plurality of draw conduits 1215 is provided, forexample, one in separate association with each of the extractionconduits 1222, 1232. Optionally, the air flowing in each of theextraction conduits 1222, 1232 is combined only at the mouthpiece. Apotential advantage of this is to allow separate control of airflowthrough each dose cartridge.

In some embodiments, a third type of conduit (not shown, but describedas a “general conduit” in, for example, a co-filed applicationdesignated “Flow Regulating Inhaler Device”, referenced hereinabove)comprises a valved conduit with a low airflow resistance when valvedopen. Optionally, a conduit of this third type is opened for admissionof ambient air during inhalation, for example to provide an advancing(or “chase”) airflow behind airflow laden with a drug substance. This isa potential advantage for moving drug substance laden air past arespiratory dead space, and/or into a deeper portion of the lungs forabsorption.

Reference is now made to FIGS. 13A-13B, which schematically illustrate alinear-type cartridge magazine 1302 and dual-dose cartridge transport1300 in two sequential positions, according to some embodiments.Reference is also made to FIGS. 13C-13D, which schematically illustratethe dual-dose cartridge transport 1300 of FIGS. 13A-13B in twosequential positions, according to some embodiments.

In each of FIGS. 13A and 13C, two pullers 2314 are shown engaged withtwo dose cartridges 2300C, 2300D, preparatory to pulling the dosecartridges 2300C, 2300D into position for substance vaporization. Ineach of FIGS. 13B and 13D, the cartridges 2300C, 2300D are shown inposition for vaporization.

In some embodiments, an inhaler device includes a clamping chamber 1300configured to clamp two or more dose cartridges 2300C, 2300D along anairflow conduit through which air flows to extract one or more drugsubstances from the dose cartridges 2300C, 2300D. Arrows 1305, 1307respectively and schematically represent airflow unladen with drugsubstance into the dose cartridges, and airflow laden with drug flow outof the dose cartridges.

In some embodiments, clamping chamber 1300 comprises two dose pullers2314 and associated dose cartridge transport mechanisms. The dosepullers 2314 are positioned to pull a dose cartridge into the cartridgetransport where they are positioned in sequence along an airflowconduit. Optionally, a clamping mechanism (not shown for clarity) isalso provided; the functions of the clamping mechanism include, forexample, electrode positioning and sealing of the airflow conduit.

In some embodiments, loading and/or heating of the dose cartridges isseparately actuatable. Optionally, one or both dose cartridges 2300C,2300D are positioned in the clamping chamber for use. Optionally, bothare positioned, but only one is heated, the two are heated at differenttimes, and/or the cartridges 2300C, 2300D are subjected to differentheating profiles (comprising time, temperature, heating rate and/oronset, for example).

Optionally, a plurality of dose cartridges 2300C, 2300D comprise asingle dose for a given inhalation. Optionally, airflow is estimated andcontrolled for the plurality of dose cartridges 2300C, 2300D in unison,essentially as described with respect to single dose cartridge clampingchamber embodiments herein.

It is noted that the temperature of air reaching a second dose cartridgealong the path is potentially higher than ambient temperature due topassage through a first heated dose cartridge. Optionally, this is takeninto account when setting a heating profile for the dose cartridges. Insome embodiments the dose cartridges are heated in sequence withdownstream doses heating before upstream ones.

Optionally, dose pullers 2314 are actuated together for dose cartridgetransport. Alternatively, each puller 2314 is actuated separately topull a specific dose cartridge from a specific location in the magazine.For example, a first dose cartridge 2300C is taken by a first puller2314 and then the dose cartridges are shifted in the magazine such thatanother dose cartridge 2300D is available at a position accessible bythe second puller 2314. Optionally, the first dose cartridge 2300C istaken when the user presses a button, positions the mouthpiece for use,or otherwise actuates the inhaler for dose cartridge transport.Optionally, the second dose cartridge 2300D is taken automatically bythe controller, or also taken up in response to the same or a secondactuation by the user.

As used herein with reference to quantity or value, the term “about”means “within ±10% of”.

The terms “comprises”, “comprising”, “includes”, “including”, “having”and their conjugates mean: “including but not limited to”.

The term “consisting of” means: “including and limited to”.

The term “consisting essentially of” means that the composition, methodor structure may include additional ingredients, steps and/or parts, butonly if the additional ingredients, steps and/or parts do not materiallyalter the basic and novel characteristics of the claimed composition,method or structure.

As used herein, the singular form “a”, “an” and “the” include pluralreferences unless the context clearly dictates otherwise. For example,the term “a compound” or “at least one compound” may include a pluralityof compounds, including mixtures thereof.

The words “example” and “exemplary” are used herein to mean “serving asan example, instance or illustration”. Any embodiment described as an“example” or “exemplary” is not necessarily to be construed as preferredor advantageous over other embodiments and/or to exclude theincorporation of features from other embodiments.

The word “optionally” is used herein to mean “is provided in someembodiments and not provided in other embodiments”. Any particularembodiment of the invention may include a plurality of “optional”features except insofar as such features conflict.

As used herein the term “method” refers to manners, means, techniquesand procedures for accomplishing a given task including, but not limitedto, those manners, means, techniques and procedures either known to, orreadily developed from known manners, means, techniques and proceduresby practitioners of the chemical, pharmacological, biological,biochemical and medical arts.

As used herein, the term “treating” includes abrogating, substantiallyinhibiting, slowing or reversing the progression of a condition,substantially ameliorating clinical or aesthetical symptoms of acondition or substantially preventing the appearance of clinical oraesthetical symptoms of a condition.

Throughout this application, embodiments of this invention may bepresented with reference to a range format. It should be understood thatthe description in range format is merely for convenience and brevityand should not be construed as an inflexible limitation on the scope ofthe invention. Accordingly, the description of a range should beconsidered to have specifically disclosed all the possible subranges aswell as individual numerical values within that range. For example,description of a range such as “from 1 to 6” should be considered tohave specifically disclosed subranges such as “from 1 to 3”, “from 1 to4”, “from 1 to 5”, “from 2 to 4”, “from 2 to 6”, “from 3 to 6”, etc.; aswell as individual numbers within that range, for example, 1, 2, 3, 4,5, and 6. This applies regardless of the breadth of the range.

Whenever a numerical range is indicated herein (for example “10-15”, “10to 15”, or any pair of numbers linked by these another such rangeindication), it is meant to include any number (fractional or integral)within the indicated range limits, including the range limits, unlessthe context clearly dictates otherwise. The phrases“range/ranging/ranges between” a first indicate number and a secondindicate number and “range/ranging/ranges from” a first indicate number“to”, “up to”, “until” or “through” (or another such range-indicatingterm) a second indicate number are used herein interchangeably and aremeant to include the first and second indicated numbers and all thefractional and integral numbers therebetween.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims.

All publications, patents and patent applications mentioned in thisspecification are herein incorporated in their entirety by referenceinto the specification, to the same extent as if each individualpublication, patent or patent application was specifically andindividually indicated to be incorporated herein by reference. Inaddition, citation or identification of any reference in thisapplication shall not be construed as an admission that such referenceis available as prior art to the present invention. To the extent thatsection headings are used, they should not be construed as necessarilylimiting.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention, which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination or as suitable in any other describedembodiment of the invention. Certain features described in the contextof various embodiments are not to be considered essential features ofthose embodiments, unless the embodiment is inoperative without thoseelements.

What is claimed is:
 1. An inhaler device comprising a clamping chamberfor an inhaler dose cartridge comprising a heat-vaporizing substance forpulmonary delivery to a user, said clamping chamber comprising: a holderhaving at least two clamping members for clamping said inhaler dosecartridge therebetween such that said heat-vaporizing substance is inalignment with an air conduit of said clamping chamber; and wherein saidholder comprises a plurality of electrodes positioned to be inelectrical contact with at least two electrical contact receivingregions of an electrically resistive heating element of said inhalerdose cartridge in the clamping chamber.
 2. The inhaler device of claim1, further comprising a cartridge transport configured to move theinhaler dose cartridge from a storage position into a use position inthe clamping chamber.
 3. The inhaler device of claim 1, wherein each ofsaid at least two clamping members comprises a portion of said airconduit.
 4. The inhaler device of claim 1, wherein at least one of saidclamping members comprises at least one air seal.
 5. The inhaler deviceof claim 1, wherein each of said clamping members comprises at least oneof said plurality of electrodes.
 6. The inhaler device of claim 5,wherein each of said at least one air seal is positioned to define asealed pathway through said inhaler dose cartridge to an exit aperture.7. The inhaler device of claim 6, wherein said electrical contact ispositioned outside the at least one air seal with respect to saidpathway.
 8. The inhaler device of claim 7, wherein said heat-vaporizingsubstance is confined to the inside of said sealed pathway.
 9. Theinhaler device of claim 4, wherein said at least one air seal comprisesan elastically deformable material.
 10. The inhaler device of claim 9,wherein said elastically deformable material is polymer rubber.
 11. Theinhaler device of claim 2, wherein the cartridge transport comprises adose pulling arm, shaped to interlock with a receiving region of theinhaler dose cartridge such that movement of the dose pulling arm movessaid inhaler dose cartridge into said use position.
 12. The inhalerdevice of claim 11, wherein said dose pulling arm is shaped to interlockwith a receiving region of the inhaler dose cartridge such that movementof the dose pulling arm moves said inhaler dose cartridge out of saiduse position and into a storage position.
 13. The inhaler device ofclaim 1, wherein said electrical contact further comprises a contactforce of about 500 N.
 14. The inhaler device of claim 1, wherein saidplurality of electrodes is shaped to contact a curved design of said atleast two electrical contact receiving regions.
 15. The inhaler deviceof claim 14, wherein said plurality of electrodes comprises a blockshaped end.
 16. The inhaler device of claim 1, wherein the holdercomprises the cartridge transport configured to move the inhaler dosecartridge.
 17. The inhaler device of claim 1, wherein said holdercomprises a body shaped and sized to engage and disengage with saidcartridge transport.
 18. The inhaler device of claim 17, wherein saidbody is cylindrical.
 19. The inhaler device of claim 17, wherein saidholder further comprises a slider mechanism configured to slide out ofsaid holder and into the inhaler dose cartridge moved by said cartridgetransport.
 20. The inhaler device of claim 1, further comprising a dosecartridge dispenser comprising a plurality of dose cartridges within aclosed container.
 21. The inhaler device of claim 2, wherein saidclamping chamber comprises: a plurality of the cartridge transports eachconfigured to move a corresponding inhaler dose cartridge; and aplurality of holders corresponding to the plurality of cartridgetransports; and corresponding electrodes for each of the cartridgetransports.